Chapter 18: regulation of gene expression

allolactose

inducer in LAC operon. And I summer of lactose formed in small amounts from lactose that enters the cell. In the absence of lactose the repressor is in its active configuration and the jeans of the operon are silenced. If lactose is added to the cells surroundings aloe lactose binds to the repressor and alters its confirmation notifying the repressor's ability to attach to the operator. This means that the operon is transcribed into mRNA for the lactose utilizing enzymes.

Basic unit of chromatin

nucleosome

histone code hypothesis

proposes that specific combinations of modifications help determine chromatin configuration and influence transcription

Bacteria often respond to environmental change by

regulating transcription. An E. coli cell living in the human: depends on the eating habits of its host. If the environment is lacking in the amino acid tryptophan which it needs to survive, the cell response by activating a metabolic pathway that makes tryptophan from another compound. Later if there is an abundance of tryptophan the bacterial cell stops producing it saving itself from squandering resources to produce a substance that is available.

Operon

the operator, the promoter, and the genes they control. The entire stretch of DNA required for enzyme production for the tryptophan pathway.

Bicoid

'Two Tailed', a defect in an embryo that results in two posterior structures (two tails, no head). An embryo his mother has two mutant alleles of the bicoid Jean lacks the front half of its body and has posterior structures at both ends this phenotype suggested that the product of the mothers gene is essential for setting up the anterior end of the fly and may be concentrated at the future anterior end of the embryo. This is an example of the Morphogen gradient hypothesis first proposed by embryologists a century ago which states that gradients of substances called morphogens establish an embryos axes and other features of its form.

Christiane Nüsslein-Volhard and wieschaus

30 years later to researchers in Germany set out to identify all the genes that affect segment formation in the fruit fly it was daunting for three reasons. One the sheer number of genes now known to be 13,700. The jeans affecting segmentation might just be a few or might be so numerous that the scientist would be unable to make sense of them. Second mutations affecting a process as fundamental a segmentation would surely be embryonic lethals mutations with phenotype is causing death at embryonic or larval stage. Because these organisms never reproduce they cannot be bred for study. They dealt with this by looking for recessive mutations which can be propagated in heterozygous flies that act as carriers. Third cytoplasmic determinants in the egg were known to play a role in axis formation so the researchers knew they would have to study the mothers genes as well as those of the embryo.

Organization of a typical eukaryotic gene

A cluster of proteins known as a transcription initiation complex as symbols on the promoter sequence at the upstream and of the gene. One of these proteins, RNA polymerize to, then proceeds to transcribe the gene synthesizing a primary RNA transcript or pre-mRNA. RNA processing includes enzymatic addition of a five prime cap in a poly a tail as well as splicing out introns to yield a mature mRNA. Associated with most eukaryotic genes are multiple control elements, segments of non-coding DNA that serve as binding sites for the proteins called transcription factors which in turn regulate transcription.

DNA methylation

A different set of enzymes can methylate certain bases in the DNA itself usually cytosine. This occurs in most plants, animals, and fungi. Long stretches of an active DNA are generally more methylated than regions of actively transcribed DNA although there are exceptions. Individual genes are usually more heavily methylated in cells in which they are not expressed. Removal of the extra muscle groups can turn some of these genes on.

Ras gene

A gene that codes for Ras, a G protein that relays a growth signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases, ultimately resulting in stimulation of the cell cycle. Normally such a path we will not operate unless triggered by the appropriate growth factor but certain mutations in the gene can lead to production of a hyperactive protein that triggers the Chinese cascade even in the absence of growth factor resulting in increased cell division. Hyperactive versions or excess amounts of any of the pathways components have the same outcome excessive cell division.

MyoD

A master regulatory gene that encodes my myod protein a transcription factor that binds to specific control elements in the enhancers of various target genes and stimulates their expression. Some target jeans for myod encode still other muscle specific transcription factors. It also stimulates expression of the myod gene itself that's perpetuating it's a factor in maintaining the cells differentiated state. Presumably all the genes activated by this gene have enhancer control elements recognized by the gene and are thus coordinately controlled. Finally the secondary transcription factors activated the genes for proteins such as myosin and actin that confer the unique properties of muscles

piwi-associated RNAs (piRNAs)

A newly discovered class of small non-coding RNAs which induce formation of heterochromatin blocking expression of some parasitic DNA elements in the genome known as trans posing's. Usually 24 to 31 nuclear tides in length they are probably processed from single-stranded are in a prepare servers. They play an indispensable role in the germ cells of many animal species where they appear to help reestablish appropriate methylation patterns in the genome during gamete formation.

MicroRNAs

A number of research studies have uncovered small single-stranded RNA molecules called micro RNAs that are capable of finding to complementary sequences in mRNA molecules. They are made from longer are in a precursors that full dock on themselves forming one or more short double-stranded hairpin structures each child together by hydrogen bonds. After each hairpin is cut away from the precursor it is trimmed by an enzyme into a short double-stranded fragment of about 22 nucleotide pairs. One of the two strands is degraded while the other forms a complex with one or more proteins. The micro RNA allows for the complex to buy into any mRNA molecule with 7 to8 nucleotides of complementary sequence. The complex then either degrades The target mRNA or blocks it's translation. It has been estimated that the expression of at least 1/2 of all human genes may be regulated by these.

Activator

A protein that binds to DNA and stimulates transcription of a specific gene. When cAMP binds to this regulatory proteins it assumes it's active shape and can attach to a specific site at the upstream end of the LAC promoter. This attachment increases the affinity of RNA polymerase for the promoter which is actually rather low even when no repressor is bound to the operator. By facilitating the binding of RNA polymerize and thereby increasing the rate of transcription the attachment of CAP to the promoter directly stimulates gene expression. This is positive regulation.

Promoter

A site where RNA polymerase can bind to begin transcription.

Differential gene expression

A typical human cell might express about 20% of its protein coding genes at any given time. Highly differentiated cells like muscle or nerve cells express a smaller fraction. Almost all of the cells in an organism contain a identical genome. However the subset of jeans expressed in each type is unique allowing them to carry out their specific function. The differences between cell types are they do not two different genes being present but to differential gene expression or the expression of different genes by cells within the same genome.

How many combinations are possible?

A very large number of combinations. A particular combination of control elements will be able to activate transcription only when the appropriate activator proteins are present which may occur at a precise time during development or in a particular cell type. This can occur because each cell type contains a different group of activator proteins.

How many changes must occur at the DNA level for a cell to become fully cancerous?

About half a dozen. These changes usually include the appearance of at least one active on to Jean in the mutation or loss of several tumor suppressor jeans. Since meet in tumor suppressor alleles are usually recessive in most cases mutations must knock out both alleles in the cells genome to block tumor suppression. Most uncle jeans behave as dominant alleles. The order of these changes is still under investigation. Technical advances in the sequencing of DNA and mRNA have allowed researchers to compare the genes in different types of tumors in different individuals. This has led to personalized cancer treatments.

Why is the human genome small?

Alternative splicing can significantly expand the repertoire of a eukaryotic genome. It was proposed as one exclamation for the surprisingly low number of human genes counted when the human genome with sequenced. The number of human genes was found to be similar to a soil worm, a mustard plant or a sea anemone This prompted questions about what accounts for the more complex morphology or external form of humans. It turns out that 75 to hundred% of human genes have multiple eggs on that probably undergo alternative spacing.

How might a proto-oncogene—a gene that has an essential function in normal cells—become an oncogene, a cancer-causing gene?

An oncogene arises from a genetic change that increases either the proto-oncogenes protein or in the intrinsic activity of each protein molecule. The genetic changes that convert proto-oncogenes to oncogenes fall into three main categories: movement of DNA within the genome amplification of a proto-oncogene and point mutations in a control element or in the proto-oncogene itself

coordinately controlled

And advantage of grouping jeans of related function into one transcription unit is that a single on off switch can control the whole cluster of functionally related genes so they are coordinately controlled.

egg-polarity genes

Another name for maternal effect genes, these genes control the orientation (polarity) of the egg, one group sets up the anterior posterior axis, while the other sets up the dorsal ventrtal axis. Like mutations in segmentation jeans mutations in maternal effect jeans are generally embryonic lethals.

Maternal mRNAs

Are crucial during development of many species. In the fruit fly gradients of specific proteins and coded by maternal mRNAs determine the posterior and anterior ends and establish the dorsal ventral axis. As the Fiamm real gross it reaches a point when the embryonic program of gene expression takes over in the maternal mRNAs must be destroyed. This involves micro RNAs. Later positional information and coded by the embryos genes operating on an ever finer scale establishes a specific number of correctly oriented segments and triggers the formation of each segments characteristic structures. When the genes operating in this final step or abnormal the pattern of the adult is abnormal.

Examples of differentiated cells making tissue specific proteins

As a result of transcriptional regulation liver cells specialize in making albumin and lens cells specialize in making Cristallin. Skeletal muscle cells invertebrates are another instructive example each is a long fiber containing many nuclei within a single pause my membrane. Skeletal muscle cells have high concentrations of muscle specific versions of the contractile proteins myosin and actin as well as membrane receptor proteins that detect signals from nerve cells.

DNA breakage and cancer

Because DNA breakage can contribute to cancer it makes sense that the risk of cancer can be lowered by minimizing exposure to DNA damaging agents such as UV radiation and chemicals in smoke. New methods were early diagnosis of cancers are being developed that rely on you techniques for analyzing and interfering with Jean expression and tumors.

How did they begin their search for segmentation genes?

By exposing Flies to eight mutagenic chemical that affected the flies gametes. They made it the mutagenized flies and then scan their descendants were dead embryos or larvae with abnormal segmentation or other defects. To find jeans that may set up the anterior posterior access they looked for embryos with abnormal ends.

How did researchers work out what happens at the molecular level during muscle cell determination?

By growing myoblasts in culture and analyzing them using molecular biological techniques. In a series of experiments they isolated different genes cause each to be expressed in separate embryonic precursor cell and then looked for differentation into Myoblasts and muscle cells. In this way they identified several master regulatory genes his protein products commit the cells to becoming skeletal muscles. Thus muscle cells are based on the expression of one or more of these master regulatory genes.

If the operator is the operon's switch how does it work?

By it's self the operon is turned on that is, RNA polymerize can bind to the promoter and transcribe the genes of the opera on. The operon can be switched off by a protein called the repressor. The repressor binds to the operon in blocks attachment of RNA polymerase to the promoter preventing transcription of the genes. A repressor protein is specific for the operator of a particular operon.

How can the rate of gene expression be strongly increased or decreased in eukaryotes?

By the binding of specific transcription factors either activators or repressor's to the control elements of enhancers. Hundreds of transcription activators have been discovered in eukaryotes. Researchers have identified two common structural elements in a large number of activator proteins: a DNA binding domain - a part of the proteins three-dimensional structure that binds to DNA- and one or more activation domains. Activation domains bind other regulatory proteins or components of the transcription machinery facilitating a series of protein protein interactions that result in transcription of a given gene.

Tumor viruses

Can cause cancer in various animals including humans. One of the earliest breakthroughs in understanding cancer came in 1911 when Peyton Rous discovered a virus that causes cancer in chickens. The Epstein-Barr virus which causes infectious mononucleosis has been linked to several types of cancer in humans including Burkitt's lymphoma. Poppy all my viruses are associated with cervical cancer and a virus called HTLV - 1. causes adult leukemia. Viruses play a role in about 15% of human cancer.

Specific types of transcription factors that function as repressors

Can inhibit gene expression in several different ways. Some repressors bind directly to control element DNA in enhancers or elsewhere, blocking activator binding or in some cases turning off transcription even when activators are bound. Other repressors block the binding of activators to proteins that allow the activators to bind DNA.

What mechanisms can lead to abnormal stimulation of the cell cycle and put the cell on the path to malignancy?

Cancer cells often are found to contain chromosomes that have broken and re-joined incorrectly trans locating fragments from one chromosome to another. If a translocated proto-oncogene ends up near an especially active promoter or other control element it's transcription may increase making it an oncogene. The second type of genetic change amplification increases the number of copies of the Proto oncogene in the south or repeated gene duplication. The third possibility is a point mutation either in a promoter or an enhancer that controls a Proto oncogene causing an increase in its expression or in the coding sequence changing the genes product to a protein that is more active or more resistant to degradation than the normal protein.

Level 2 of metabolic control

Cells can adjust the production level of a certain enzyme they can regulate the expression of the genes encoding the enzymes. The song can't stop making the enzymes that catalyze the synthesis of tryptophan. In this case the control of the enzymes occurs at the level of transcription the synthesis of messenger RNA coding for these enzymes. Many genes of the bacterial genome are switched on or off by changes in the metabolic status of the cell. One basic machanism for this control of gene expression described as the operon model was discovered in 1961.

Where do these processes have their base?

Cellular behavior. Even morphogenesis, the shaping of the organism can be traced back to changes in the shape motility and other characteristics of the cells that make up various regions of the embryo. Almost all cells in an organism have the same genome therefore differential gene expression results from jeans being regulated differently in each cell type.

What does coordinate control of dispersed genes often occur in response to?

Chemical signals from outside the cell. For example a steroid hormone enters a cell and binds to a specific intracellular receptor proteins forming a hormone receptor complex that serves as a transcription activator. Every gene his transcription is stimulated by a particular steroid hormone regardless of its chromosomeOr location has a control element recognized by that hormone receptor complex this is how estrogenactivatesAGroupOfGenesThatStimulateCellDivisionInuterineCellsPreparingTheUterusForPregnancy.

Regulation of transcription initiation

Chromatin-modifying enzymes provide initial control of gene expression by making a region of DNA either more or less able to bind the transcription machinery. Once the chromatin of a gene is optimally modified for expression the initiation of transcription is the next major step at which gene expression is regulated. As in bacteria the regulation of transcription initiation in eukaryotes involves proteins that bind to DNA and either facilitate or inhibit binding of RNA polymerize. The process is more complicated and eukaryotes.

Maternal affect gene

Cytoplasmic determinants in the egg are the substances that initially establish the axes of the fruit fly body. These substances are encoded by genes of the mother called maternal effect of jeans. These are genes that one mute and in the mother result in a mutant phenotype in the offspring regardless of the offsprings and genotype. In fruit fly development the mRNA or protein products of maternal effect jeans are placed in the egg while it is still in the mothers ovary. When the mother has a mutation in such a gene she makes a defective gene product or not at all in her eggs are defective when they are fertilized they fail to develop properly.

How does E Coli sense that the glucose concentration is low? and Relay it to the genome?

Depends on the interaction of an allosetic regulatory protein with a small organic moleucle (cyclic AMP=cAMP), which accumulates when glucose is scarce; the regulatory protein is called catabolite activator protein (CAP) is an activator

Muscle cells

Develop from embryonic precursor cells that have the potential to develop into a number of cell types including cartilage in fat cells but particular conditions commit them to being muscle cells. Although the committed cells appear unchanged under the microscope determination has occurred and they are now myoblasts. Eventually myoblasts start to turn out large amounts of muscle specific proteins in fused to form mature elongated multi nucleate skeletal muscle cells.

When glucose and lactose are present

E. coli preferentially uses glucose. The enzymes for glucose breakdown in glycolysis are continually present. Only when glucose is in short supply and lactose is present does E. coli use lactose as an energy source and only then does it synthesize appreciable quantities of the enzymes for lactose breakdown.

Tryptophan synthesis pathway

E. coli synthesizes the amino acid tryptophan from a precursor molecule and a multi step pathway. Yuch reaction in the pathways capitalize by specific enzyme and the five jeans that code for the subunit of these enzymes are clustered together on the bacterial chromosome. Single promoter serves all five genes which together constitute a transcription unit. This transcription gives rise to one long mRNA molecule that codes for the five polypeptides making up the enzymes in the tryptophan pathway. The seller can translate this one mRNA into five separate polypeptides because it is punctuated with stuff and start codons that so you know where the coding sequence for each polypeptide begins and ends.

Transcription factories

Each chromosome in the interphase nucleus occupies a distinct territory. Recently techniques have been developed that allow researchers to cross link and identify regions of chromosomes that associate with each other during interphase. These studies reveal that lives of chromatin extend from individual chromosome all territories into specific sites in the nucleus. Different loops from the same chromosome and lupus from other chromosomes may congregate in such sites some of which are rich in RNA polymerize and other transcription associated proteins. These are called transcription factories.

Homeotic genes discovery

Edward Lewis in the 1940s showed the value of the genetic approach to studying the fly he studied bazaar mutant flies with developmental defects that lead to ask your wings or legs in the wrong place. He located the mutations on the fly is genetic map connecting the developmental abnormalities to specific genes this supplied the first concrete evidence that gene somehow directed the developmental process. The genes he discovered are called homeotic genes and control pattern formation in the late embryo larva and adult.

Drosophila body

Fruit flies and other arthropods have modular construction, and ordered series of segments that make up the bodies three major parts: the head, the thorax from which the wings and legs extend, in the abdomen. Like other bilaterally symmetrical animals it has an anterior posterior axis (head-tail), a dorsal ventral axis (back-belly) in a right left axis. In the fly cytoplasmic determinants that are localize in the unfertilized egg provide positional information for the placement of anterior posterior and dorsal ventral axes even before fertilization.

Repressable enzymes

Generally function in anabolic pathways which synthesize essential and products from raw materials or precursors. By suspending production of an end product when it is already present insufficient quantities this song can allocate it's organic precursors and energy for other things.

What are the final opportunities for controlling gene expression?

Happens after translation often eukaryotic polypeptides must be processed to yield functional protein molecules. Cleavage of the initial insulin polypeptide forms the active hormone. In addition many proteins undergo chemical modifications making them functional. Regulatory proteins are commonly activated or in activated by the reversible edition of phosphate groups and proteins destined for the surface of animal cells acquire sugars. So surface proteins and many others must also be transported to target destinations in the cell in order to function. Regulation may occur any of these steps involved in modifying or transporting.

p53 gene

If there is a signal that leads to the synthesis of a protein that surprises the cell cycle, the signal could be damage to the cells DNA perhaps as the result of exposure to ultraviolet light. Operation of the signaling pathway box the cell cycle until the damage has been repaired. Otherwise the damage might contribute to tumor formation by causing mutations or chromosomal abnormality's. That's the jeans for the components of the pathway act as tumor suppressor jeans. The P 53 Jean names for the 53000 Dalton molecular weight of its protein product is a tumor suppressor Gene. The protein it encodes is a specific transcription factor that promotes the synthesis of cell cycle inhibiting proteins that is why am mutation that knocks it out can lead to excessive cell growth and cancer.

When does this happen?

In all organisms a common controlpoint for gene expression is that transcription regulation at this stage often occurs in response to signals coming from outside the cell like hormones. For this reason Jean expression is often equated with transcription for both bacteria and eukaryotes but the greater complexity of eukaryotic cell structure and function provides opportunities at many additional stages.

How does the eukaryotic cell Deal with jeans of related function that need to be turned on or off at the same time?

In bacteria these coordinately control genes are often clustered into an operon which is regulated by a single promoter and transcribed into a single mRNA molecule. The genes are expressed together in the encoded proteins are produced concurrently. With a few minor exceptions operons that work this way have not been found in eukaryotes.

Combination of control elements

In eukaryotes the precise control of transcription depends largely on the binding of activators to DNA control elements. The number of completely different nucleotide sequence is found and control elements is surprisingly small considering the great number of jeans that must be regulated in a typical eukaryotic cell. A dozen or so short nucleotide sequence is appear again and again in the controls elements for different jeans. On average each enhancer is composed of about 10 control elements each which can bind only one or two specific transcription factors. It is the particular combination of control elements in enhancer associated with a gene rather than the presence of a single unique control element that is important.

Methylation and genomic imprinting

In some species DNA methylation seems to be essential for the long term in activation of jeans that occurs during normal cell differentiation in the embryo. Experiments have shown that deficient DNA methylation leads to abnormal embryonic development in organisms such as meis and mustard plants. Once methylated jeans usually stay that way through successive subdivisions in a given individual. DNA sites were one strand is already methylated enzymes methylate the correct daughter strand after each round of DNA replication. They are just passed on insoles forming specialized tissues keep a chemical record of what occurred during embryonic development. A methylation pattern maintain this way accounts for genomic and printing. Where methylation permanently regulates expression of either the maternal or paternal allele.

History of understanding these patterns

In the early 20th century embryologist made detailed anatomical observations of embryonic development but it did not reveal the specific molecules that guy development or determine how patterns are established. In the 1940s scientist began using the genetic approach the study of millions to investigate fruit fly development. These studies have established that genes control development and have led to an understanding of roles that specific molecules play.

Where does pattern formation begin in animals?

In the early embryo when the major axes of an animal are established. Before the tissues and organs of a bilaterally symmetrical animal appear the relative positions of the animals head and tail right and left sides and back in front are set up that's establishing the three major body axes.

correpressor

In this system tryptophan functions as a cobra Prosser, a small molecule that cooperates with the repressor proteins to switch and operon off. As it accumulates more tryptophan molecules associate with the repressor molecules which can then bind to the operator and shut down production of the tryptophan pathway enzymes. If the cells tryptophan level drops transcription of the operons genes resumes. This operon is one example of how gene expression can respond to changes in the external in internal environment.

Genes that normally regulate cell growth and division during the cell cycle

Include jeans for growth factors, their receptors, and the intracellular molecules of signaling pathways. Mutations that alter any of these genes in somatic cells can lead to cancer. The agent can be random spontaneous mutation however it is likely that many result from environmental influences.

Epigenetic inheritance

Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance. Where is mutations in the DNA are permanent changes, modifications to the chromatin can be reversed by processes that are not fully understood. The molecular systems for chromatin modification may interact with each other in a regulated way. And drosopholia experiments have suggested that a particular history on modifying enzyme recruits a DNA methylation enzyme to one region and that the two enzymes collaborate to silence a set of genes. Proteins have also been found that first bind to methylated DNA and then recruit histone deacetylation enzymes.

What else does CAP do?

It helps to regulate other operons that encode enzymes used in catabolic pathways. It may affect the expression of more than 100 genes in E. coli. When glucose is plentiful and CAP is an active the synthesis of enzymes that catalyze compounds other than glucose generally slows down. The ability to catabolize other compounds such as lactose enables a cell deprived of glucose to survive. The compounds present in the cell at the moment determine which operons are switched on the result of simple interactions of activator and repressor proteins with the promoters of the genes in question.

Why was bicoid research groundbreaking?

It led to the identification of a specific protein required for some of the earliest steps in pattern formation and helped us to understand how different regions of the egg can give rise to cells that go down different developmental pathways. It increased our understanding of the mothers critical role in the initial phases of embryonic development. Finally the principle that a gradient of morphogens can determine polarity and position is a key developmental concept for a number of species.

Inducible enzymes

Lactose. usually function in catabolic pathways; their synthesis is induced by a chemical signal. Usually function in catabolic pathways which breakdown a nutrient to simpler molecules. By producing the appropriate enzymes only when the nutrient is available the cell avoids wasting energy.

What about ones that don't enter the cell?

Many signaling molecules such as non-steroid hormones and growth factors bind to receptors on the cell surface. These molecules can control Jean expression indirectly by triggering signal transduction pathways that lead to activation of particular transcription activators or repressor's. Coordinate regulation in such pathways is the same as were steroid hormones jeans with the same control elements are activated by the same chemical signals. Systems for coordinating gene regulation probably arose early in evolutionary history.

distal control elements (enhancers)

May be thousands of nucleotides upstream or downstream of a gene of a gene or even within an intron. A given gene may have multiple enhancers each active at a different time or in a different cell types or location in the organism. Each however is generally associated with only that gene and no other.

Why does the incidence of cancer increase greatly with age?

More than one somatic mutation is generally needed to produce all the changes characteristic of a fully fledged cancer cell. If cancer results from accumulation of mutations and mutations occur throughout life then the longer we live the more likely we are to develop cancer.

How does cancer run in families?

Multiple genetic changes are required to produce a cancer cell. An individual inheriting oncogene or a mutant tumor suppressor gene is one step closer to accumulating the necessary mutations.

What determines mRNA lifespan?

Nucleotide sequence is found in the untranslated region at the three prime end of the molecule. Researchers transferred such a sequence from the short-lived mRNA for a growth factor to the three prime end of a normally stable globin. The globe in mRNA was quickly degraded. Other mechanisms that degrade or block expression of mRNA molecules have come to light. These involve an important group of newly discovered RNA molecules that regulate gene expression at several levels.

Egg Cytoplasm Determinant

One important source of information early and development. It contains both RNA and proteins and coded by the mothers DNA. The cytoplasm of an on fertilized egg is not homogeneous. Messenger RNA proteins, other subjects and organelles are distributed on evenly in the unfertilized ag and this has a profound impact on the development of the future embryo. Maternal substances in the ad that influence the course of early development are called cytoplasmic determinants. After fertilization early mitotic divisions distribute the zygote cytoplasm into separate cells. The nuclei of the cells made the speak supposed to different set of cosmic determinants depending on the portion it received. The combination helps determine its developmental fate by regulating expression of the cells jeans during the course of different Tatian.

Colorectal cancer

One of the best understood types of human cancer. About 135,000 new cases are diagnosed each year in the US and it causes 60,000 deaths each year. Like most cancers it develops gradually. The first sign is often a polyp, a small benign growth in the colon lining. The cells of the polyp look normal although they divide unusually frequently the tumor grows in May eventually become malignant invading other tissues. The development of a tumor is paralleled by gradual accumulation of mutations that convert proto-oncogenes to oncogenes and knockout tumor suppressor genes. A ras oncogene and a mutated P 53 tumor suppressor gene are often involved.

Addition of methyl or phosphate groups to histone tails

Other chemical groups can be reversibly attached to amino acid's in histone tails. Addition of methyl groups or histone methylation can promote condensation of the chromatin well addition of a phosphate group or phosphorylation to an amino acid next to a methylated amino acid can have the opposite effect. Led to hypothesis.

Non-coding RNA and other shit

Protein coding DNA accounts for only 1.5% of the human genome and a similarly small percentage of the genomes of many other multicellular eukaryotes. Very small fraction of the nonprotein coding DNA consists of jeans for RNA such as ribosomal RNA and transfer RNA. Until recently most of the remaining DNA was assumed to be on transcribed because it did not specify proteins or the few types of known RNA and that it did not contain meaningful information. However a flood of recent data has contradicted this. An in-depth study of a region comprising one percent of the human genome should that more than 90% of that region was transcribed. Entrance accounted for only a fraction of this transcribe non-translated RNA. These and other results suggest that a significant amount of the genome may be transcribed into non-protein coding RNAs including a variety of small RNAs. Many questions remain unanswered.

Mediator proteins

Protein mediated bending of the DNA is thought to bring the bound activators into contact with a group of mediator proteins which intern interact with proteins at the promoter. These multiple protein protein interactions help assemble in position the initiation complex on the promoter. A study show that the proteins regulating a mouse globin Gene contact both the genes promoter and and and hands are located about 50,000 nucleotides upstream.

Alternative RNA splicing

RNA processing in the nucleus in the export of mature RNA to the cytoplasm provide several opportunities for regulating gene expression that are not available in prokaryotes. In alternative splicing different mRNA molecules are produced from the same primary transcript depending on which are in a segments are treated as examines and which as entrance. Regulatory proteins specific to a cell type control intron exon choices by binding to regulatory sequences within the primary transcript.

RNA blocking specific genes

Recent experiments have shown that related RNA based mechanisms may also block the transcription of specific genes. Some plant micro RNA's have sequences that bind to gene promoters and can repressed transcription and piRNAs can block expression of specific genes. Some cases have been reported of activation of Jean expression by both.

Regulation by non-coding RNA's

Regulation by both small and large is known to occur at several points in the pathway of gene expression including mRNA translation and chromatin modification. Two types of small non-coding RNAs have been extensively studied and they were the focus of the 2006 Nobel prize.

Negative control of genes

Regulation of both operons involves the negative control of jeans because the operons are switched off by the active form of the repressor protein. Allolactose induces enzyme synthesis not by acting directly on the genome but by freeing the operon from the negative affect of the repressor. Jean regulation is said to be positive only when a regulatory proteins interacts directly with the genome just switch transcription on.

small interfering RNA (siRNA)

Researchers have found that injecting double-stranded our name all yours into a cell somehow turned off expression of a gene with the same sequence as the RNA they called this phenomenon RNA interference and was later showing to be due to small interfering RNAs. These are similar in size and function to micro RNAs. Subsequent research showed that the same cellular machinery generates both in that both can't associate with the same proteins producing similar results. The distinction is based on the nature of the precursor molecule for each. Multiple small interfering RNAs are forms from a much longer when you're double-stranded are in a molecule.

Why doesn't it work on all kinds of cell?

Researchers have shown that the myod protein is even capable of changing some kinds of fully differentiated non-muscle cells such as fat cells and liver cells into muscle cells however when likely explanation is that activation of the muscle specific genes is not solely dependent on myod but requires a particular combination of regulatory proteins some of which are lacking in cells that do not respond. The determination and differentiation in other tissues may happen the same way.

How does a zygote become an organism

Results from three into related processes cell division so different Tatian and morphogenesis. Three series of my ptotic subdivisions the zygote gives rise to a large number of cells. Cell division alone would merely produce identical cells during embryonic development sells not only increase in number but also undergo cell differentation the process by which cells become specialize in structure and function. Moreover the different cells are not randomly distributed but are organize into tissues and organs in a particular three-dimensional arrangement.

Chromatin remodeling

Small RNAs can cause a remodeling of chromatin structure. In some yeasts small interfering RNA is produced by the yeast cells themselves are required for the formation of heterochromatin at the centromere's of chromosomes. According to one model and RNA transcript produced from DNA in the centromerif region of the chromosome is copied into double-stranded RNA by a yeast enzyme and then processed into small interfering RNA is. These then associate with a complex of proteins and act as a homing device targeting the complex back to RNA transcript being made from the center America sequences of DNA. Once there proteins in the complex recruit enzymes that modify the chromatin turning it into highly condensed heterochromatin found at the centromere.

Other types (indirect)

Some activators and repressers act indirectly by affecting chromatin structure. Studies using yeast and mammalian cells show that some activators recruit proteins that acetylate his stones near the promoters of specific genes that's promoting transcription. Some repressors recruit proteins that deacetylate histones leading to reduce transcription referred to as silencing. This seems to be the most common mechanism of oppression in eukaryotes.

What are the functions of the protein products of tumor suppressor genes?

Some tumor suppressor proteins repair damaged DNA a function that prevents the self from accumulating cancer causing mutations other tumor suppressor proteins control the adhesion of cells to each other or to the extracellular matrix; proper cell encourage is crucial to in normal tissues and is often absent in cancers. Others are components of cells are going pathways that inhibit the cell cycle.

Viruses and siRNAs

Some viruses have double-stranded are in a Gino's because the cellular RNAi pathway can lead to the destruction of our Ines with sequences complementary to those found in double-stranded RNAs this pathway may have evolved as a natural defense against infection by such viruses. However the fact that RNA interference can also affect the expression of nonviral cellular jeans may reflect a different evolutionary origin. Moreover many species including members apparently produce their own long double-stranded are in a precursors to small RNAs such as siRNAs Once produce these RNAs can interfere with gene expression at stages other than translation.

Proto-oncogenes

Subsequently close counterparts of viral oncogenes were found in the genomes of humans and other animals the normal versions of the cellular genes are called proto-oncogenes or proteins that stimulate normal growth and division.

co-expressed eukaryotic genes

Such as genes coding for the enzymes of a metabolic pathway are typically scattered over different chromosomes. In these cases coordinate Jean expression depends on the association of a specific combination of control elements with every gene of a dispersed group. The presence of these elements can be compared to the raised flags on a few mailboxes out of money signaling to the carrier to check these boxes. Copies of the activators that recognize the control elements fine to them promoting simultaneous transcription of the genes no matter where they are in the genome.

Why are histones able to be modified?

The N terminus of each histone molecule in a nucleosome Protrudes out words from the nucleus own. These tales are accessible to various modifying enzymes that catalyze the addition or removal of specific chemical groups.

Why is the operon not switched off permanently?

The binding of oppressors two operators is reversible. And operator vacillates between two states one without the repressor bound and one with. The relative duration of each state depends on the number of active repressor molecules. Second the trp repressor like most regulatory proteins is an Alistair protein with two alternative shapes active and in active. It is synthesize in an in active form with little affinity for the operator. Only if tryptophan binds to the repressor at an allosteric site does the repressor protein change to the active form that can turn the operon off.

What happens if the amount of glucose increases

The cAMP concentration falls and without it CAP detaches from the opera. Because CAP is inactive, RNA polymerize binds less efficiently to the promoter and transcription of the lac operon proceeds only at a low level even in the presence of lactose. Thus the lac operon is under dual control negative control by the lack repressor and positive controlled by CAP. The state of the lack repressor determines whether or not transcription of the lack operon genes occurs at all the state of CAP controls the rate of transcription if the operon is repressor free.

Lactose

The disaccharide lactose milk sugar is available to E. coli in the human: if the host drinks milk. Lactose metabolism begins with the hydrolysis of the disaccharide into its component monosaccharides glucose and galactose this reaction is catalyzed by the enzyme beta galactosidase. Only a few molecules of this enzyme are present in an E. coli growing in the absence of lactose however if it is added the number of beta galactosidase molecules in the cell increases 1000 fold within 15 minutes.

Determination

The earliest changes that set a cell on a path to specialization are subtle ones showing up only at the molecular level. Before a biologist knew much about the molecular changes occurring in embryos they coined the term determination to refer to the events that lead to the observable differentation of a cell. Once it has undergone determination and embryonic cell is irreversibly committed to its final fate. If a committed cell is experimentally place in another location it will still differentiate into the cell type that it normally would.

Fruit Fly lifecycle

The egg develops in the females over he surrounded by ovarian cells called nurse cells and Follicle sales. This supports our supply the egg with nutrients mRNAs and other substances needed for development and make the egg shell. After fertilization and laying of the egg embryonic development results in the formation of a segmented larva which goes through three marvel stages. Then the fly larva forms a cocoon.

What is the other major source of developmental information?

The environment around a particular cell. Most influential are the signals impinging on an embryonic cell from other embryonic cells in the vicinity including contact with cell service molecules on neighboring cells and growth factors secreted by neighboring cells. These signals cause changes in the target cells a process called induction. The molecules conveying the signals within the target sell our cell surface receptors and other proteins express by the embryos own jeans. In general the signaling prep molecules send a self down a specific developmental path by causing changes in its Jean expression that eventually result in cellular changes.

Lac operon

The gene for a beta galactosidase is part of the lac operon which includes two other genes encoding for enzymes that function in lactose utilization. The entire transcription unit is under the command of one main operator and promoter. The regulatory gene, lacI located outside the operon codes for an allosteric repressor protein that can switch off the operon by binding to the operator. Unlike trp. This repressor is active by it self binding to the operator and switching the operon off. In this case a specific small molecule called in inducer in activates the repressor.

Specific transcription factors

The interaction of general transcription factors and RNA polymerize to what the promoter usually leads to only a low rate of initiation and production of a few RNA transcripts. In eukaryotes high levels of transcriptions of particular genes at the appropriate time in place depend on the interaction of control elements with another set of proteins which can be thought of as specific transcription factors.

Selective degradation

The length of time each protein functions in the cell is strictly regulated by means of selective degradation. Many proteins such as the cyclones involved in regulating the cell cycle must be relatively short-lived if this song is the function appropriately. To mark a particular protein for destruction this all commonly attaches molecules of a small protein called ubiquitin to the protein. Giant protein complexes called proteasomes then recognize the ubiquitin tagged proteins integrate them. The importance is under scored by the finding that mutations making specific cell cycle proteins impervious to degradation can lead to cancer.

mRNA lifespan differences

The lifespan of mRNA molecules in the cytoplasm is important in determining the pattern of protein synthesis in a cell. Bacterial mRNA molecules typically are degraded by enzymes within a few minutes of their synthesis. This short lifespan is one reason bacteria can change their patterns of protein synthesis so quickly in response to environmental changes. MRNAs in multicellular eukaryotes typically survive for hours, days, or even weeks. The mRNAs for the hemoglobin polypeptides in developing red blood cells are unusually stable and these long-lived mRNAs are translated repeatedly in the cells.

positional information

The molecular cues that control pattern formation. Provided by cytoplasmic determinants and inductive signals. They tell a cell it's location relative to the body axes and neighboring cells and determine how the cell and its progeny will respond to future molecular signals.

tissue-specific proteins

The outcome of determination, observable cell different Tatian is marked by the expression of genes for tissue specific proteins. These are found only in a specific cell type and give the cell its characteristic structure and function. The first evidence of different Tatian is the appearance of mRNAs for these proteins. Eventually different Tatian is observable with a microscope as changes in cellular structure. On the molecular level different sets of genes are sequentially expressed in a regulated manner as new cells arise from division of their precursors. A number of the steps in gene expression may be regulated during different Tatian with transcription among the most important. In the fully differentiated cell transcription is still the principal regulatory point.

morphogens

The physical processes that give an organism its shape. Means creation of form.

What happens once the P 53 gene has been activated for example by DNA damage?

The protein functions as an activator for several other jeans. Often it activates a gene called P 21 whose product holds the cell cycle by binding cycling dependent kinases allowing time for the cell to repair the DNA. Researchers recently showed that it also activates expression of a group of micro RNA's which in turn inhibit the cell cycle. Also the protein can turn on jeans directly involved in DNA repair. Finally when DNA damages are irreparable it activates Suicide genes Who is proteins bring about a pop ptosis. It acts in several ways to prevent a cell from passing on mutations due to DNA damage. If mutations do accumulate in the south survives through many divisions which is more likely if the P 53 tumor suppressor gene is defective cancer may ensue.

What generates the first differences among cells in an early embryo? And what controls the differentiation of all the various cell types as development proceeds?

The specific genes expressed in any particular cell of a developing organism determine its path. Two sources of information used to bearing extends in different species tell a cell which genes to express at any given time.

Regulation of chromatin structure

The structural organization of chromatin not only packs a cells DNA into a form that fits in the nucleus but also helps regulate gene expression in several ways. The location of the genes promoter relative to nuclear zones into the sites where the DNA attaches to the chromosome scaffold or nuclear lamina can affect whether the gene is transcribed. In addition jeans without heterochromatin which is highly condensed are usually not expressed. Lastly certain chemical modifications to the histone proteins into the DNA of chromatin can influence both chromatin structure and gene expression.

How does this happen?

The transcription factors of a cell must locate the right genes at the right time when Jean expression proceeds abnormally serious and balances and diseases including cancer can arise.

repressible operon

The trp operon is said to be repressible because it's transcription is usually on but can be inhibited or repressed when a specific small molecule binds allosterically to a regulatory protein.

Level 1 of Metabolic Control

There are two levels. First cells can adjust the activity of enzymes already present. This is a fast response which relies on the sensitivity of many enzymes to chemical cues that increase or decrease their catalytic activity. The activity of the first enzyme in the tryptophan synthesis pathway is inhibited by the pathways and product this is feedback inhibition and it's typical of anabolic or biosynthetic pathways allowing us all to adapt to short term fluctuations in the supply of a substance it needs.

Nuclear architecture

There is a new model of a nucleus with a defined architecture and regulated movements of chromatin. Relocation of particular genes from the chromosomal territories to transcription factories may be part of the process of readying genes for transcription.

The importance of epigenetic variation

There's more evidence of the importance of epigenetic information in the regulation of gene expression. They might help explain why one identical twin acquires a genetically based disease such as schizophrenia but the other does not despite their identical genomes. Alterations in normal patterns of DNA methylation are seen in some cancers where they are associated with inappropriate gene expression.

Are MRNAs most important?

These discoveries hint at a large diverse population of RNA molecules in the cell that play crucial role in regulating gene expression. We must revise our long-standing view that because mRNAs code for proteins they are the most important.

How do viruses cause cancer?

They can interfere with gene regulation if they integrate their genetic material into the DNA of a cell. Viral integration may donate an oncogene to the cell, disrupt a tumor suppressor gene or convert a Proto oncogene into an oncogene. In addition some viruses produce proteins that inactivate P 53 and other tumor suppressor proteins making the cell more prone to becoming cancerous.

Were they successful

They eventually identified about 1200 Jeans essential for pattern formation during embryonic development. Of these about 120 were essential for normal segmentation later the researchers were able to group these jeans by general function to map them and to clone many of them for further study in the lab. They received the 1995 Nobel prize.

Is the bicoid product a protein called by bicoid in fact a more fission that determines the anterior end of the fly? Are the mRNA and protein products of these genes located in the egg in a position consistent with the hypothesis?

They found that bicoid mRNA is highly concentrated at the extreme interior end of the mature egg as predicted. After the egg is fertilized the mRNA is translated into proteins this protein then diffuses from the interior and towards the posterior resulting in a gradient of protein within the early embryo with the highest concentration at the interior. Scientist injected pure bicoid mRNA into various regions of early embryos the protein that resulted from its translation caused anterior structures to form at the injection sites.

Alternative RNA splicing examples

This gene encodes two different proteins. Other genes offer possibilities for a far greater number of products. Researchers have found a drosophilia with enough alternatively spliced eggs on is to generate about 19,000 membrane proteins with different extracellular domains. At least 94% of the alternative mRNA are actually synthesized. Each developing nerve cell in the fly appears to synthesize a unique form of the protein which acts as an identification badge on the cell surface.

General transcription factors

To initiate transcription in eukaryotic RNA polymerize requires the assistance of transcription factors. Some are essential for the transcription of all protein coding genes therefore they are often called general transcription factors. Only a few general transcription factors independently bind a DNA sequence such as the Tata box within the promoter the other is primarily buying proteins including each other and are in a polymerize too. Protein protein interactions are crucial to the initiation of eukaryotic transcription. Only when the complete initiation complex has assembled can the polymerize begin to move along the DNA template strand producing a complementary RNA strand.

Translation initiation regulation

Translation is another opportunity for regulating gene expression this occurs most commonly at the initiation stage. For some mRNAs the initiation of translation can be blocked by regulatory proteins that bind to specific sequences or structures within the untranslated region at the five prime or three prime end preventing the attachment of ribosomes. A different mechanism is seen in a variety of mRNA is present in the eggs of many organisms. Initially these stored mRNAs lack poly a tail is of sufficient link to allow translation initiation. At the appropriate time during embryonic development a cytoplasmic enzyme adds more adenine nucleotides allowing translation initiation.

Global control

Translation of all the mRNAs in a cell maybe regulated simultaneously. In a eukaryotic cells this global control usually involves the activation or in activation of one or more of the protein factors required to initiate translation. This mechanism plays a role in starting translation of mRNAs that are stored in eggs. Just after fertilization translation is triggered by the sudden activation of translation initiation factors. The response is a burst of synthesis of the proteins and coded by the stored mRNAs. Some plants and algae store mRNAs during periods of darkness late then triggers the reactivation of the translation apparatus.

Operator

When an E. coli cell must make its own tryptophan all the enzymes for the metabolic pathway are synthesized at one time the switch is a segment of DNA called an operator. Positioned within the promoter or in some cases between the promoter and the enzyme coding genes the operator controls the access of RNA polymerase to the genes.

Oncogenes

cancer causing genes. Cancer research led to the discovery of cancer causing genes in certain types of viruses.

Pattern formation

cytoplasmic determinants and inductive signals both contribute to the development of a spatial organization in which the tissues and organs of an organism are all in their characteristic places this is called ___ ___.

Operon model

discovered in 1961 by Francois Jacob and Jacques Monod at the Pasteur institute in Paris; the basic mechanism for this control of gene expression in bacteria

Proximal control elements

located close to the promoter sometimes considered part.

How do different sets of activators come to be present in the two cells?

material placed in egg by mother triggers sequential program of gene regulation that occurs as cells divide; this program makes the cells different from each other in a coordinated fashion.

histone acetylation

the attachment of acetyl groups (-COCH3) to certain amino acids of histone proteins, the chromatin becomes less compact, and the DNA is accessible for transcription. Aceto-groups are attached to life scenes in histone tails; do you acetylation is the removal. When the light scenes are acetylated their positive charges are neutralized in the history entails no longer find your neighboring nuclear zones. This promotes the folding of chromatin into a more compact structure when this binding does not occur chromatin has a looser structure as a result transcription proteins have easier access to genes in acetylated region. Researchers have shown that some enzymes us in the way or do you civilly histones are closely associated with or even components of transcription factors that bind your promoters. Do you suggest that histone acetylation enzymes may promote the initiation of transcription not only by changing structure but also by binding to and that's recruiting components of the transcription machinery.

regulatory gene

the trp repressor is the product of a _____ ______ called trpR, which is located some distance away from the operon it controls and has its own promoter. Regulatory genes are expressed continuously although at a low rate.

Inducible operon

usually off, but can be stimulated (induced) when a specific small molecule interacts with a regulatory protein (example lac operon)

Evolutionary significance of small ncRNAs

• small ncRNAs can regulate gene expression at multiple steps • an increase in the number of miRNAs in a species may have allowed morphological complexity to increase over evolutionary time • siRNAs may have evolved first, followed by miRNAs and later piRNAs (which are only found in animals many thousand of them so allows potential for v sophisticated gene regulation) Big roles in embryonic development.