Chapter 18
Maternal effect genes
genes of the mother that code for proteins or mRNA that are deposited in unfertilized egg
Lactose
has glucose, E. coli can break it down into glucose and galactose-uses an inducable system
inducer
inactivates the repressor
inducer
inactivates the repressor (tryptophan no longer present) This system saves energy!
Negative Regulation
inhibits
embyronic lethals
mutations with phenotypes causing death at the embryonic or larval stage
inducable genes
on normally, but no reason for them to be on normally
tissue-specific proteins
proteins are found only in a specific cell type and give the cell its chracteristic structure and function; first evidence of differentiation is the apperance of mRNAs for these proteins; different sets of gene are sequentially expressed in a regulated manner as new cells arise form divisions of their precursos
Proteasomes
recognize ubiquitin-tagged proteins and degrade them.
Positive gene regulation
regulatory protein interacts directly with the genome to switch transcription on
Silencing
repressors recruting proteins that deacetylate histones, leading to reduced transcription
Control elements
segements of noncoding DNA that help regulate transcription by binding certain proteins
Lack of gene expression
No mRNA and no protein
DNA methylation
reduces transcription
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Complete review
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Bicoid research
1. Led and proved the presence of proteins required for some of the earliest step in pattern formation 2. Increased our understanding of the mother's critical role in initial phases of embryonic development 3. Gradient morphogens that can determine polarity and position is a key developmental concept for a number of species
Animal axes system
All determined by cytoplasmic determinant shape of human established as soon as it is fertilized
Why are fruit fly maternal effect genes also called egg-polarity genes?
Because their products, made and deposited into the egg by the mother, determine the head and tail ends as well as the back and belly of the embryo
Repressor
Can switch off the operon (protein) blocks attachment of RNA polymerase to the promoter , preventing transcription of its genes; specific for the operator of a particular operon regulatory TrpR that is far away that makes a repressor (makes mRNA); made in an inactive form; if you eat trpR, it binds to the inactive repressor and and activates it which it then attaches to the operator and shuts it down)
Tumor-suppressor genes
Cells contain genes whose normal products inhibit cell division because the proteins they encode help prevent uncontrolled cell growth.
As you learned in chapter 12, mitosis gives rise to two daughter cells that are genetically identical to the parent cell. Yet you, the product of many mitotic divisions are not composed of identical cells, why?
Cells undergo differentiation during embryonic development, becoming different from each other; in the adult organism, there are many highly specialized cell types
Development from Egg to Larva
Egg develops in ovary Eggs are surrounded by nurse cells and follicle cells These cells supply the egg with nutrients, mRNA, proteins to make egg shell After the egg is fertilized, embryonic development results in the formation of a segmented larva until it develops into adult fruit fly
Inherited Predisposition to Cancer
Geneticists are devoting much effort to identifying inherited cancer alleles so that predisposition to certain cancers can be detected early in life. About 15% of colorectal cancers, for example, involve inherited mutations.
Gene Amplification
In this very unusual process, the normal DNA replication process is seriously flawed. The result is that instead of making a single copy of a region of a chromosome, many copies are produced The genes on each of the copies can be transcribed and translated, leading to an overproduction of the mRNA and protein corresponding to the amplified genes as shown below. The squiggly lines represent mRNA being produced via the transcription of each copy of the gene.
Does gene regulations stop?
No- Even when an organism is fully developed, gene expression is fully regulated in a similarly fine-tuned manner Any changes in the expression of one or few genes can lead to development of cancer
Bicoid gene
One maternal effect gene (egg- polarity gene, because they determine axes) is called Bicoid gene (two-tailed) encodes a protein (morphogen) that determine head structures Hypothesis: Bicoid normally encodes for a morphogen that specifies head (anterior) end of the embryo Prediction: If this is true, then the Bicoid mRNA and its encoded protein should be localized in the anterior of the egg Results: only find the Bicoid mRNA where the head should be! Make a mutant, where the mother is defective for this bicoid gene; the mutant has two tails =no headdevelopment Indicates morphigenous define the polarity of the egg
Fruit fly pattern formation
The body consist of a series of segments grouped into the head, thorax and abdomen Determined by positional information provided by cytoplasmic determinants in unfertilized egg When you build a building, first you have to decide where will be the front and where will be the back of the building. multi-cellular organisms must have a body plan Anterior-posterior (head-to-tail) axis Dorsal-ventral (back-to-belly) axis Right-left axis
Types of cells associated with cancer
The genes that normally regulate cell growth and division during the cell cycle include Genes for growth factors Growth factor receptors And the intracellular molecules of signaling pathways. Mutations that alter any of these genes in somatic cells can lead to cancer.
How might a proto-oncogene—a gene that has an essential function in normal cells—become an oncogene, a cancer-causing gene?
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
What is the main mode of controlling gene expression?
Transcription
Viruses in cancer
Viruses seem to play a role in about 15% of human cancer cases worldwide. Viruses contribute to cancer development by integrating their genetic material into the DNA of infected cells. By this process, a retrovirus may donate an oncogene to the cell.
maternal effect genes
a gene that when a mutant in the mother, results in a mutatn phenotype in the offspring, regardless of the offspring's own genotype When a mother has a mutation in such a gene, she makes a defective gene product and her egg is defective=can fail to develop properly
Activator
a protein that binds to DNA and stimulates transcription of a gene
egg-polarity genes
because maternal effect genes also control the orientation of hte egg and consequently of hte fly, maternal effect genes are also called egg-polarity genes One group of these genes sets up the anterior-posterior axis of the embryo, while a second group establishes the dorsal-ventral axis; mutations in maternal effect genes are generally embryonic lethals
The signaling molecules released by an embryonic cell can induce changes in a neighboring cell without entering the cell. How?
by binding to a receptor on the receiving cell's surface and triggering a signal transduction pathway that affects gene expressions
oncogenes
cancer causing genes Subsequently, close counterparts of these oncogenes were found in the genomes of humans and other animals.
protoncogenes
code for proteins that stimulate normal cell growth and division
homeotic genes
control pattern formation in the late embryo, larva, and adult
morphogenesis
creation of form the physical process that gives an organism its shape
What are the substances that initially determine the axes of the body?
cytoplasmic determinants; these substances are encoded by genes of the mother, fittingly called maternal effect genes
Repressible system
(anabolic pathway); ceasing production of a specific enzyme, in response to the presence of a specific substrate (metabolite) in the environment If tryptophan is present (if it is bound allosterically to a regulatory protein) (in E. Coli) pathway is turned off It is always on, but can be inhibited
Mechanisms of Post-transcription regulation
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Regulation of metabolic pathway in bacteria
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What if?
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add pgs. 358
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RNAi
...injecting double stranded RNA molecules into a cell somehow turned off expression of a gene with the same sequence as the RNA
Gene regulation results in dramatic changes that require three processes
1. cell division (increase in cell number) 2. cell differentiate (cell specialization in structure and function) 3. Morphogenesis (creation of form or body shape) All cell activities depends on gene expression on production of proteins all three have their basis in cellular behavior;
How genes regulated?
1.Chromatin Histone acetylation DNA methylation 2. Transcription Alternative RNA splicing mRNA degredation (sequences of 3' end of RNA) 3. Translation blocking binding of mRNA to ribosome microRNA (miRNA), inhibits initiation stage interference RNA (siRNA) Chromatin remodeling 4. Protein Post translational modification
Organizaiton of typical eukaryotic gene
A eukaryotic gene adn the DNA elements that control it are organized like 18.8 Transcription initiation complex: assembles on the promoter sequence at het upstream end of the gene; one of these proteins, RNA polymerase II, then proceeds to transcribe the gene, synthesizing a primary RNA transcript RNA processing includes enzymatic addition of a 5' cap and a poly-A tail Control elements Associated with most eukarytoic genes are multiple control elements, segments of noncoding DNA that help regulate transcription by binding certain proteins
Activator
A protein that binds to DNA and stimulates transcription of a gene when cAMP binds to a regulatory protein, CAP assumes its active shap eand can attach to a speciic site on the upstream end of the lac promoter; this attachmetn increases the affinity of RNA polymerase for ht epromoter, amount of glucose rises as glucose rises, the cAMP falls, and with out cAMP CAP detaches from the operon and becomes inactive and RNA polymerase binds less efficiently to the promoter
A model for the action of enhancers and transcription activators
Activator proteins bind to distal control elements grouped as an enhancer in the DNA A DNA binding protein brings the bound activators closer to the promoter The activators bind to transcription factors and mediator proteins and help them form active transcription initiator complex on promoter
DNA Methylated
Addition of methyl groups to certain bases in DNA after DNA is synthesized. In fact, the DNA of most plants and animals has methylated bases, usually cytosine. Inactive DNA, such as that of inactivated mammalian X chromosomes, is generally highly methylated compared with DNA that is actively transcribed
Initiation of translation
Another opportunity for regulating gene expression; most commonly at hte initiation stage; initiation of translation of some mRNA can be blocked by regulatory proteins that bind to specific sequences or structures within the ultranslated region at the 5' cap and the poly-A tail of an mRNA molecules FINISH REVIEWING
Natural selection of bacteria
Bacterial cells that conserve resources and energy have a selective advantage over cells that are unable to do so natural selection has favored bacteria that express only the genes whose products are needed by the cell Ex. E coli Such feedback inhibition, typical of anabolic pathways, allows a cell to adapt to short-term fluctuations in supply of a substance it needs (if eating the necessary amino acid, won't turn on the pathway to make that pathway- E. Coli thrive off tryptophan; but if not eating it, will turn pathway on)
Gene regulation in prokaryotes
Better understood & simpler than eukaryotic gene regulation •In prokaryotes, genes coding for proteins in a pathway are grouped together & controlled by the same regulation - called operons Main source of energy: ATP; (starting from glucose); First choice for bacteria is glucose (uses glycolysis and oxidative phosphorylation to make ATP)
Cell type-specific transcription factors
Both liver cells and lens cells have the genes for making the proteins albumin and crystallin, but only liver cells make albumin (a blood protein) and only lens cells make crystallin (the main component of the lens of the eye). The specific transcription factors (activators and repressors) made in a particular type of cell determine which genes are expressed. Collection of their activator and repressor proteins Eye cells do not let albumin gene to express The differences between cell types, therefore, are due not to different genes being present, but to differential gene expression, the expression of different genes by cells with the same genome
Compare and contrast miRNAs and siRNAs
Both: are small, single-stranded RNAs that associate with a complex of proteins adn then can base-pair with mRNAs that have a complementary sequence; this pairing leads to degradation or an end of translation; processed from double-stranded RNa precrusors by the enzyme Dicer miRNAS are encoded by genes int eh cell's genome siRNAs arise form longer stretch of double stranded RNA
Inducible system
Catabolic pathway; production of a specific enzyme in response to the presence of substrate; If lactose is present, the pathway turns on Usually off but cam be turned on
Chaperone vs protoseomes
Chaperone=fold proteins Protoseomes=destroy proteins
Histone modification
Chemical modifications to histones play a direct role in the regulation of gene transcription. The N-terminus of each histone molecule in a nucleosome protrudes outward from the nucleosome. These histone tails are accessible to various modifying enzymes, which catalyze the addition or removal of specific chemical groups. In histone acetylation, acetyl groups (—COCH3) are attached to positively charged lysines in histone tails Deacetylation is the removal of acetyl groups. When the histone tails of a nucleosome are acetylated, their positive charges are neutralized and they no longer bind to neighboring nucleosomes Histone acetylation enzymes may promote the initiation of transcription not only by modifying chromatin structure, but also by binding to, and "recruiting," components of the transcription machinery. Acetylation enzymes may promote the initiation of transcription via binding and recruiting components of transcription.
Eukarytoic gene expression can be regulated at any stage!
Control of gene expression is in response to internal or external environments And to create specialized cells All cells have the same genome Differences in cells with the same genome are the result of differential gene expression (amount of functional protein that is made) A typical human cell expresses about 20% of its genes at a given time; highly differentiated cells, such as muscle or nerve cells express an even smaller fraction of their genes; the subset of genes expressed in cells of each type is unique, allowing these cells to cary out their spedific function
How a cell knows where to go to do its job?
Cytoplasmic determinants and inductive signals both contribute to the development of a spatial organization (arrangement in space) in which the tissues and organs are all in their characteristic places This process called pattern formation Cytoplasmic determinants in egg are encoded by sets of genes called maternal effect genes Because these genes control orientation (polarity) of the egg and the organism, they are also called egg-polarity genes (establish anterior-posterior, dorsal-ventral and right-left axis in embryo)
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
What generates the first differences among cells in an early embryo? How do different sets of activators come to be present in two cells?
Differences among cells arise from the egg's cytoplasm 1. Cytoplasmic determinants (maternal substances, regulate gene expression which determine its developmental fat) 2. Inductive signals and interaction between embryonic cells via cell surface molecules (cause changes in target cells, induction)
MicroRNAs REVIEW pg. 365
During the past few years, another mechanism that blocks expression of specific mRNA molecules has come to light; researchers have found small-single stranded RNA molecules called microRNA's that can bind to complementary sequences in mRNA molecules The miRNAs are formed from longer RNA precursors that fold back on themselves, forming a long, double-stranded hairpin structure held together by hydrogen bonds. An enzyme called Dicer cuts the double-stranded RNA molecule into short fragments. One of the two strands is degraded, and the other strand (miRNA) associates with a large protein complex and acts as a homing device, directing the complex to any mRNA molecules that have the complementary sequence. The miRNA-protein complex then either degrades the target mRNA or blocks its translation.
Stages in gene expression of eurkaryotes
Each stage is a potential control point at which gene expression can be turned on or off or accelerated or slowed down
Body plan
For the tissues to function effectively all over, its three d arrangement must be established and superimposed on the differentiation process
Compare the roles of general and specific transcription factors in regulating gene expression.
General transcription factos function in assembling the transcription initiation complex at the promoters for all genes; specific transcription factos bind to control elements associated with a particular gene and either decerase or increase transcription of the gene
Genome of prokaryotes vs. eukaryotes
Genome of prokaryotes •In prokaryotic genomes, most of the DNA codes for protein, tRNA, or rRNA •The small amount of noncoding DNA consists mainly of regulatory sequences, such as promoters. •The coding sequence of nucleotides along a prokaryotic gene proceeds from start to finish without interruption by noncoding sequences (introns). Genome of eukaryotes •In eukaryotic genomes most of the DNA does not encode protein or RNA, and it includes more complex regulatory sequences. •In fact, humans have 10,000 times as much noncoding DNA as prokaryotes. •Some of the noncoding DNA in multicellular eukaryotes is present as introns within genes. Indeed, introns account for most of the difference in average length between human genes and prokaryotic genes.
In general, what is the effect of histone acetylation and DNA methylation on gene expression?
Histone acetylation is associated with gene expression; DNA methylation is associated with lack of expression
Most important question in biology
How a fertilized egg develops into a full-term animal or human? Somatic cell division should produce genetically identical cells; but how come the cells in our body have different structures and function
A program of differential gene expression leads to the differential cell types in a multicellular organism
In embryonic development of multicellular organisms, a fertilized egg (zygote) gives rise to cells of many different types, each with a different structure and corresponding funciton; cells are organized into tissues, organs, organ system, and then the whole organisms Any developmental program must produce cells of different types that form higher-level structures arranged in a particular way
Combinational control of gene activation
In eukaryotes, the precise control of transcription depends largely on teh binding of activators to DNA control elemnts; considering the great number of genes that must be regulated ina typical animal or plant cell, the number of completely different nucelotide sequences found in control elements is small Combination of control elements in an enhancer associated with a gene turns out to be more important than the presence of a single unique control element
Inducible vs. Repressible operons
Inducible are catabolic and Repressible are anabolic (use energy)
Epigenetic inheritance
Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence The chromatin modifications that we have seen do not entail a change in the DNA sequence; yet they may be passed along to future generations of cells; inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance DNA mutations are permanent Chromatin can be reversed May explain why one identical twin gets a genetically based disease and the other one doesn't;
What happens when glucose and lactose are present in E. Coli enviornment?
It prefers glucose; the enzymes for glucose breakdown in glycolysis are continually present. Only when lactose is present and glucose is in short supply does E. Coli use lactose and only then does it synthesize enzymes necessary for lactose breakdown
Regulatory Gene
Located some distance from the operon it controls and has its own promoter; regulatory genes are expressed continuously at a low rate Why not turned off permanetely? The binding of repressors to operators is reversible (an operator vacillates between two states-one with out the repressor bound and one with the repressor bound; the relative duration of each state depends on the active number of repressors) and trp the repressor is an allosteric protein with two altnernative shapes (active and inactive); the trp repressor is synthesized in an inactive form with little affinity for the trp operator
Genomic imprinting
Methylation permanently regulate gene expression of either maternal or paternal allele of a particular gene at the start of development
Regulation of Transcription initiation
Once chromatin has been modified for expression, the initiation of transcription is the next major step at which gene expression is regulated
Alternative RNA splicing
RNA processing in the nucleus and the export of mature RNA to the cytoplasm provide several opportunities for regulating gene expression that are not available in prokaryotes. Different mRNA moleucles are produced from the same primary transcript, depending on which RNA segments are treated as exons and which are introns; The primary transcripts of some genes can be spliced in more thanone way, generating different mRNA molecules. Notice in this example that one mRNA molecule has ended up with the green exon and the other with the purple exon.
Regulation of Chromatin structure
Regulation of chromatin Structure (Histone Code Hypothesis: change in chromatin pattern, shape and transcription chromatin modification includes DNA unpacking which involves histone acetylation CO-CH3 (increase gene expression) and DNA methylation (inhibit gene expression) Heterochromatin (highly condensed chromatin) Methylation of histones condenses the chromation but phosphorylation next to methylation undoes that effect chromatin modification includes DNA unpacking which involves histone acetylation and DNA methylation 6 billion base pairs in our genome DNA of eukartyoic cells is packaged with proteins in an elaborate complex known as chromatin (basic until which is the nucleosome; packs cell's DNA into a compact form, and regulates gene expression Location of genes protmoter's relative to nucleosomes and to the sites where the DNA attaches to the chromosomes scaffold or lamina can affect whether the gene is transcribed or not If have heterochromatin=not expressed! (repressive) Certain modifications to the histones and DNA of chromatin can influence both chromatin structure and gene expression
Mechanisms of Action of Repressors
Some specific transcription factors function as repressors to inhibit expression of a particular gene. Eukaryotic repressors can cause inhibition of gene expression in several different ways. block the binding of activators either to their control elements or to components of the transcription machinery. Other repressors bind directly to their own control elements in an enhancer and act to turn off transcription even in the presence of activators
Operator
Switch segment of DNA Turned on: RNA polymerase can bind to the promote rand transcribe the genes of the operon, but can be turned off by a repressor
Central dogma
The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. •It states that information cannot be transferred back from protein to either protein or nucleic acid. DNA information always transferred to RNA to protein
Protein processing and degradation
The final opportunities for controlling gene expression occur after translation; Many proteins undergo chemical modifications that make them functional Regulatory proteins are commonly activated or inactivated by the reversible addition of phosphate groups, and proteins destined for the surface of animal cells acquire sugars; Cell surface proteins and many others must also be transported to target destinations in the cell in order to function Even if you make the protein, there is a way to stop; proteasome is like a blender it breaks down the protein and stops them Proteasome works like a blender!= denatures it A protein must be tagged or labeled with a structure like ubiquitin (small protein), so the proteasome knows to destroy it
Suppose you compared the nucleotide sequences of the distal control elements in the enhancers of three genes that are expressed only in muscle tissue. What would you expect to find? Why?
The three genes should ahve some similar or identical sequences in the control elements of their enhancers; because they are simliar the same specific transcription factors could bind to the enhancers of all three genes and stimulate their expression coordinately
DNA methylation and histone deacetylation
These two result in lack of transcription = more condensation and less transcription Comparison of the same genes in different tissues shows that the genes are usually more heavily methylated in cells in which they are not expressed. Removal of the extra methyl groups can turn on certain of these genes. Researchers have discovered that certain proteins that bind to methylated DNA recruit histone deacetylation enzymes. Thus, a dual mechanism, involving both DNA methylation and histone deacetylation, can repress transcription.
Corepressor
Trp functions in this system; a small molecule that cooperates with a repressor protein to switch an operon off; as tryptophan accumulates, more tryptophan molecules associate with trp repressor molecules, which can then bind to the trp operator and shut down production of the tryptophan pathway enzymes
Metabolic control
Two levels: First, cells can adjust the activity of enzymes already present; fairly fast response that relies on sensitivity of many enzymes to chemical cues that increase or decrease their catalytic activity Second, cells can adjust the production level of certain enzymes; they can regulate the expression of the genes encoding the enzymes; operon model
Environment
another major source of development information is the enviornment around a particular cell; most influential are the signals impinging on an embryoinc cell from other embryonic cells int eh vicinity, including contact with cell-surface molecules on neighboring cells and the binding of growth factors secreted by neighboring cells ; such signals cause changes in target cells (induction)
How does binding of the trp corepressor and the lac inducer to their respective repressor proteins alter repressor function and transcription in each case
binding by the trp corpresspor activates the trp repressor, shutting off the trp operon; binding by the lac inducer inactivates the lac repressor; leading to transcription of the lac operon
miRNAs
capable of binding to complementary sequences in mRNA molecules ; miRNAs are formed from longer RNA precursors that fold back on themselves, forming one or more short double-stranded hairpin structures held together by hydrogen bonds; after each hairpin is cut away from the precursor, it is trimmed by an enzyme into short double-stranded fragment of about 20 pairs miRNA protein complex either degrades the target mRNA or blocks its translation
A certain mutation in E. Coli changes the lac operator so that the active repressor cannot bind. How would this affect the cell's production of B galactosidase ?
cell would continuously produce B galactosidase adn the two other enzymes for lactose utilization even in the absence of lactose thus wasting cell resources
Fertilized egg to a catepole
cells go through mitotic cell divisions, cell differentiation, and morphogensis; why fertilized egg goes to this structure
induction
changes in target cells; the molecules conveying these signals within the target cell are cell-surface receptors and other proteins expressed by the embryo's own genes Normally signaling molecules send a cell down a specific developmental path by causing changes in its gene expression that eventually result in observable cellular changes Thus, interactions between embryonic cells help induce differentiation of the many specialized cell types making up a new organisms
Thousands of genes, but only a small amount of DNA
codes for proteins (1.5% in humans) ; rest codes for RNA products or isnt trascribed at all; the transcription factos of a cell must locate the right genes at the right time; when this goes array serious problems can happen
CAP
cyclic AMP; (accumulates when glucose is scarce) How does ecoli cell sense the glucose concentration and relay this information to the genome?: depends on interaction of an allosteric regulatory protein with a small organic molecule, cAMP regulatory protein is called CAP=activator
Once mRNA encoding a particular protein reaches the cytoplasm, what are four mechanisms that can regulate the amount of the protein that is active in the cell?
degradation of the mRNA, regulation of translation, activation of the protein, and protein degradation
enhancers
distant distal control elements, may be thousands of nucleotides upstream or downstream of a gene or even within an intron a given gene may have mutliple enhancers each active at different times or in a different cell type ; Each enhancer is associated with only one gene Rate of gene expression can be increased or decreased by the binding of proteins, either activators or repressors to the control elements of enhancers
muscle cell developments
from myoblasts; from embryonic precursor cells that have the ptoential to develop into a number of cell types
repressible enzyme
function in anabolic pathways, which synthesize essential end products from raw materials (precurosrs); by suspending production of an end product, when it is already present in a sufficient amont, the cell can allocate its organic precursors and energy for other uses) = avoid wasting energy!
Operon
group of genes regulated together and controlled by an on/off switch called operator operator, the promoter (several genes under 1 control), and the genes they control (the entire stretch of DNA required for enzyme producting) E Coli growth depends on amino acid of trypthophan; if absent, repressor inactive, and opeon is on Picture: repressor example Downstream: end of genes Upstream: promoter; regulatory TrpR that is far away that makes a repressor (makes mRNA); made in an inactive form; if you eat trpR, it binds to the inactive repressor and and activates it which it then attaches to the operator and shuts it down)
mediator protein
interacts with proteins at the promoter; protein-mediated bending of the DNA is through to bring bound activators in contact with mediator proteins mutliple protein to protein interactions help assemble and position the initiation complex on the promoter
lac operon
lactose (milk sugar) is available to E. Coli in the human colon, if the host drinks milk; lactose metabolism begins with hydrolysis of the disaccharide into its component monosaccharides, glucose and galactose, a reaction catalyzed by B-galactosidase Only a few moleucles of htis enzyme are present in an E Coli cell growing with out lactose normally ; if lactose is added to the bacterium's environment, however, the number of B-galactosidase molecules int eh cell increases thousandfold in 15 minutes. Gene for B galactosidase is part of the lac operon, which includes two other genes coding for enzymes that function in lactose utilization; entire transcription unit is under the command of a single operator and promoter LacI, located outsie the operon, codes for all allosteric repressor protient aht can swtich off lac operon (in active form) lac repressor is in active form (different) binding to the operator and switching the lac operon off; in this case a specific small molecule inactivtes the repressor (inducer) With out being bound to the repressor, the lac operon is trascirbed into mRNA for lactose-utilizing enzymes
mRNA degradation
life span of mRNA molecules in the cytoplasm is important in determining the pattern of protein synthesis in a cell Bacteria mRNA molecules are typically degraded by enzymes within a few minutes; such short life span of mRNA is one reason bacteria can change their patterns of protein synthesis so quickly in response to environmental changing mRNAs in eukartyoes can last up to weeks
acetylation
loosen chromatin structure and enhance transcription decetylation=decrease transcription
Gene expressed
mRNA made-→protein produced pic repressor example Tryptophan is made at the end of the pathway at A Genes of operon lead up until
Cytoplasmic determinants
maternal substances in the egg that influence the course of early development After fertilization, early mitotic divisions distribute the zygote's cytoplasm into separate cells; the nuclei of these cells may thus be exposed to different cytoplasmic determinants , depending on which portions of zygotic cytoplasm was received The combination of cytoplasmic determinants in a cell helps determine its development fate by regulating expression of the cell's genes during the course of cell differentiation
coordinated control of dispersed genes
often occurs in repsonse to chemical signals from outside the cell ex. steroid hormones operons that work this way (genes being expressed together) have been been found in eukartyotic cells
siRNAs
smaller than miRNAs,formed by much longer double-stranded RNA molecules, each of which give rise to many si RNAs
Enhancers for specific transcription factors
specific transcription factors that function as repressors can inhibit gene expression in several different ways; some repressors bind directly to control element DNA, blocking activator binding or, in some cases, turning off transcription even when activators are bound Some activators and repressors act indirectly by affecting chromatin structure silencing: repressors recruting proteins taht deacetylate histones, leading to reduced transcription
inducible enzymes
synhtesis is induced by chemical signal (ex. allolactose)
Determination
the events that lead to the observable differentiation of a cell (before scientists knew about molecule changes occuring in embryos) ;once it had undergone determination, an embryonic cell is irreversibly committed to its final fate we understand determination in terms of molecular changes make tissue-specific proteins
Differential gene expression
the expression of different genes by cells with the same genome; differences between cell types are not due to different genes, but due to differential gene expresison
Role of transcription factor
the initiate transcription, eukaryotic RNA polymerase requires the assistance of proteins called transcription factors General transcription factors: essential for the transcription of all protein-coding genes Protein-protein interactions are crucial to the initiation of eukarytoic transcription Only when the complete initiation complex has assembled can the polymerase begin to move along the DNA template strand, producing a complementary strand of RNA specific transcription factors: high levels of transcription of particular genes at the appropriate time and place depend on the interaction of control elements with another set proteins
positional information
the molecular cues that control pattern formation; are provided by cytoplasmic determinants and inductive signals; these cues tell a cell its location relative to the body axes and to neighboring cells and determine how the cell and its progeny will respond to future molecular signals Scientists studied Drosophilia, and studied mutants to look at development established that genes control development and have led to an understanding of the key roles that specific moleucles play in defining position and directing differential
Negative controls of genes
the operons are switched off by active form of the repressor protein
cell differentiation
the process by which cells become specialized in structure and function; the different kinds of cells are not randomly distributed but are organized into tissues and organs in a particular three-arrangement
What generates the first differences among cells in early embryo?
the specific genes expressed in any particular cell of a developing organism determine its path; two sources of information tell a cell which genes to express at any given time during embryonic development One important source is the egg's cytoplams (contains RNA and proteins encoded by mother's DNA); cytoplasm of an unfertilized egg is not homogeneous; mRNA, proteins, other substances, and organelles are distributed unevenly in the unfertilized egg, and this unevenness has a profound impact on the development of the future embryo in many species
Pattern formation
the two processes of cytoplasmic determinants (protein and RNA) and induction contribute to pattern formation (morphogenesis) For animals, begins in early embryo, when the major axes of an animal are established; before tissues and organsappear, the relative positions of the animals head and tial etc are set up, thus establishing the boyd's three major body axes
Common control point for transcription
transcription Regulation at thsi stage is often in response to signals coming from outside the cell like hormones or other signaling molecules; gene expression is equated with trnascription for both bacteria and eukaryotes
UTR
untranslated region 3'--->degradation 5'---> inhibition of translation (in order to shorten RNA this 5' cap needs to be removed; nuclease enzyme can rapdily chew up the mRNA
