BIO CHPT 18 Textbook Reading
chromatin
-DNA of eukaryotic cells is packaged with proteins in an elaborate complex -basic unit of which is the nucleosome -helps regulate gene expression in several ways
Eukaryotic regulation of gene expression
-RNA processing in the nucleus & the export of mature RNA to the cytoplasm provide opportunities -ex. @ RNA-processing level: alternative RNA splicing -ex. @ export of mature RNA to the cytoplasm: initiation of translation or after translation
regulatory gene
-a gene that codes for a protein, such as a repressor, that controls the transcription of another gene or group of genes
maternal effect gene
-a gene that, when mutant in the mother, results in a mutant phenotype in the offspring, regardless of the offspring's genotype -AKA egg-polarity genes -were first identified in Drosophila melanogaster -control the orientation (polarity) of the egg and consequently that of the fly -two groups of these genes set up the anterior-posterior and dorsal-ventral axes of the embryo -like mutations in segmentation genes, mutations in maternal effect genes are generally embryonic lethals
cytoplasmic determinant
-a maternal substance, such as a protein or RNA, that when placed into an egg influences the course of early development by regulating the expression of genes that affect the developmental fate of cells -combination of these in a cell helps determine its developmental fate by regulating expression of the cell's genes during the course of cell differentiation
RNA interference (RNAi)
-a mechanism for silencing the expression of specific genes -double-stranded RNA molecules that match the sequence of a particular gene are processed into siRNAs that either block translation or trigger the degradation of the gene's messenger RNA -happens naturally in some cells and can be carried out in laboratory experiments as well -can process double-stranded RNAs into homing devices that lead to the destruction of related RNAs, some scientists think that this pathway may have evolved as a natural defense against infection by such viruses -can also affect the expression of nonviral cellular genes may reflect a different evolutionary origin for the RNAi pathway
embryonic lethal
-a mutation with a phenotype leading to death of an embryo or larva
binding domain
-a part of the protein's three-dimensional structure that binds to DNA
induction
-a process in which a group of cells or tissues influences the development of another group through close-range interactions
activator
-a protein that binds to DNA and stimulates gene transcription -in prokaryotes, activators bind in or near the promoter -in eukaryotes, activators generally bind to control elements in enhancers -indirectly affect chromatin structure -some recruit proteins that acetylate histones near the promoters of specific genes, thus promoting transcription
repressor
-a protein that inhibits gene transcription -in prokaryotes, repressors bind to the DNA in or near the promoter -in eukaryotes, repressors may bind to control elements within enhancers, to activators, or to other proteins in a way that blocks activators from binding to DNA -binds to the operator, preventing RNA polymerase from transcribing the genes, often by preventing RNA polymerase from binding -turns off operon -specific for the operator of a particular operon -encoded by a regulatory gene -some repressors bind directly to control element DNA (in enhancers or elsewhere), blocking activator binding; other repressors interfere with the activator itself so it can't bind the DNA -indirectly affect chromatin structure -some recruit proteins that remove acetyl groups from histones, leading to reduced transcription, meaning the genes are silenced
enhancer
-a segment of eukaryotic DNA containing multiple distal control elements -given gene may have multiple, each active at a different time, cell type, or location in the organism -each is generally associated with only that gene and no other -rate of gene expression can be strongly increased or decreased by the binding of specific transcription factors, either activators or repressors, to the control elements of _________ -composed of about ten control elements, each binding only one or two specific transcription factors -the particular combination of control elements in an ______ is associated with a gene, rather than a single unique control element, that is important in regulating transcription of the gene
control element
-a segment of noncoding DNA that helps regulate transcription of a gene by serving as a binding site for a transcription factor -multiple control elements are present in a eukaryotic gene's enhancer
corepressor
-a small molecule that binds to a bacterial repressor protein and changes the protein's shape, allowing it to bind to the operator and switch an operon off -more molecules, bind to operator, shut down production -one example of how gene expression can respond to changes in the cell's internal and external environment
microRNA (miRNA)
-a small, single-stranded RNA molecule, generated from a double-stranded RNA precursor -associates with one or more proteins in a complex that can degrade or prevent translation of an mRNA with a complementary sequence -a single-stranded RNA of about 22 nucleotides that forms a complex with one or more proteins -allows the miRNA-protein complex to bind to any mRNA molecule with at least seven or eight nucleotides of complementary sequence, the complex then degrades the target mRNA or, less often, simply blocks its translation -approximately 1,500 genes for this in the human genome -expression of at least one-half of all human genes may be regulated by this
inducer
-a specific small molecule that binds to a bacterial repressor protein and changes the repressor's shape so that it cannot bind to an operator, thus switching an operon on
operon
-a unit of genetic function found in bacteria and phages, consisting of a promoter, an operator, and a coordinately regulated cluster of genes whose products function in a common pathway -regulated by a single promoter and transcribed into a single mRNA molecule
histone tails
-accessible to various modifying enzymes that catalyze the addition or removal of specific chemical groups
chromosome conformation capture techniques
-allow researchers to cross-link and identify regions of chromosomes associating with each other during interphase -the territory of each chromosome is divided into regions of chromatin loops (topologically associated domains, or TADs), within which chromatin sites associate mainly with each other -loops of chromatin, each likely a TAD, extend from individual chromosomal territories into specific sites in the nucleus -different loops from the same chromosome and loops from other chromosomes may congregate in such sites, some of which are rich in RNA polymerases and other transcription-associated protein (*transcription factories*), thought to be areas specialized for a common function
long noncoding RNA (lncRNA)
-an RNA between 200 and hundreds of thousands of nucleotides in length that does not code for protein but is expressed at significant levels -almost 28,000 known; 20,000 were functional and that some were associated with specific diseases -responsible for X chromosome inactivation, which prevents expression of genes located on one of the X chromosomes in most female mammals -transcripts of the XIST gene located on the chromosome to be inactivated -bind back to and coat that chromosome, leads to condensation of the entire chromosome into heterochromatin -involve chromatin remodeling in large regions of the chromosome -act as a scaffold, bringing DNA, proteins, and other RNAs together into complexes; these associations may act either to condense chromatin or, in some cases, to help bring the enhancer of a gene together with mediator proteins and the gene's promoter, activating gene expression in a more direct fashion
Translation
-another stage where gene expression is regulated, most commonly at the initiation stage -initiation of this in mRNA can be blocked by regulatory proteins that bind to specific sequences or structures within the untranslated region (UTR) at the 5‵or 3‵ end, preventing the attachment of ribosomes -all the mRNAs in a cell may be regulated simultaneously -in eukaryotic cell, such "global" control usually involves the activation or inactivation of one or more protein factors required to initiate translation -plays a role in starting this in mRNAs that are stored in eggs -just after fertilization, this is triggered by the sudden activation of translation initiation factors, the response is a burst of synthesis of the proteins encoded by the stored mRNAs -some plants and algae store mRNAs during periods of darkness; light then triggers the reactivation of the translational apparatus
homeotic gene
-any of the master regulatory genes that control placement and spatial organization of body parts in animals, plants, and fungi by controlling the developmental fate of groups of cells
activation domains
-bind other regulatory proteins or components of the transcription machinery -facilitating a series of protein-protein interactions that result in enhanced transcription of a given gene
signaling molecules
-bind to receptors on a cell's surface and never actually enter the cell -can control gene expression indirectly by triggering signal transduction pathways that activate particular transcription factors -
structural domains of transcription activators groupings
-binding domain -activation domains
miRNAs and siRNAs
-can associate with the same proteins, producing similar results -are RNA molecules that are mostly double-stranded
metabolic pathway regulation
-cells can adjust the activity of enzymes already present, a fairly rapid physiological response, which relies on the sensitivity of many enzymes to chemical cues that increase or decrease their catalytic activity -cells can adjust the production level of certain enzymes via a genetic mechanism; that is, they can regulate the expression of the genes encoding the enzymes; the control of enzyme production occurs at the level of transcription, the synthesis of messenger RNA from the genes that code for these enzymes -feedback inhibition, typical of anabolic (biosynthetic) pathways, allows a cell to adapt to short-term fluctuations in the supply of a substance it needs
transcription initiation complex
-cluster of proteins -assembles on the promoter sequence at the "upstream" end of the gene
Regulatory proteins
-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 -regulation might occur at any of the steps involved in modifying or transporting a protein
egg's cytoplasm
-contains both RNA and proteins encoded by the mother's DNA -unfertilized: not homogeneous -mRNAs, 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
genes
-control development and have led to an understanding of the key roles that specific molecules play in defining position and directing differentiation
proximal control elements
-control elements located close to the promoter
distal control elements
-control elements located far from the promoter -may be thousands of nucleotides upstream or downstream of a gene or even within an intron
model of a nucleus
-defined architecture and regulated movements of chromatin -unexpressed genes are located in the outer edges of the nucleus -expressed genes are found in its interior region -relocation of particular genes from their chromosomal territories to transcription factories in the interior may be part of the process of readying genes for transcription
tissue-specific proteins
-determination in terms of molecular changes that result in observable cell differentiation that is marked by the expression of genes for this -give the cell its characteristic structure and function
alternative RNA splicing
-different mRNA molecules are produced from the same primary transcript -depending on which RNA segments are treated as exons and which as introns (regulatory proteins specific to a cell type control intron/exon choices by binding to regulatory sequences within the primary transcript) -can significantly expand the repertoire of a eukaryotic genome -was proposed as one explanation for the surprisingly low number of human genes counted when the human genome was sequenced -more than 90% of human protein-coding genes likely undergo alternative splicing -the extent of this greatly multiplies the number of possible human proteins, which may be better correlated with complexity of form than the number of genes
chromatin modifications
-do not change the DNA sequence -may be passed along to future generations of cells -mutations in the DNA are permanent changes -modifications to the chromatin can be reversed -respond more rapidly to environmental conditions
combination of control elements
-each can activate transcription only when the appropriate transcription activators are present, which may occur at a precise time during development or in a particular cell type -just a few can allow differential regulation of transcription, this can occur because each cell type contains a different group of transcription activators
cell specialization
-each cell type must maintain a specific program of gene expression in which certain genes are expressed and others are not
RNA processing
-enzymatic addition of a 5′cap and a poly-A tail -splicing out of introns -to yield a mature mRNA
general transcription factors
-essential for the transcription of all protein-coding genes -few bind to a DNA sequence, such as the TATA box in most promoters, but many bind to proteins, including other transcription factors as well as RNA polymerase II
Robert Waterland and Randy Jirtle
-feeding methyl groups to the mothers at a key time during gestation led to a change in gene expression in the offspring's phenotype -extent of the color shift correlated with the level of DNA methylation
specific transcription factors
-for genes not expressed all the time, meaning they are regulated -the interaction of general transcription factors and RNA polymerase II with a promoter usually leads to a low rate of initiation and production of few RNA transcripts from genes that are not expressed at significant levels all the time or in all cells -in eukaryotes, high levels of transcription of these particular genes at the appropriate time and place depend on the interaction of control elements with another set of proteins
Repressible enzymes
-generally function in anabolic pathways, which synthesize essential end products from raw materials (precursors) -by suspending production of an end product when it is already present in sufficient quantity, the cell can allocate its organic precursors and energy for other uses
transcription
-gives rise to one long mRNA molecule that codes for the five polypeptides making up the enzymes in the tryptophan pathway (cell can translate this one mRNA into five separate polypeptides because the mRNA is punctuated with start and stop codons that signal where the coding sequence for each polypeptide begins and ends) -protein-protein interactions are crucial to the initiation of eukaryotic __________
operator
-in bacterial and phage DNA, a sequence of nucleotides near the start of an operon to which an active repressor can attach -the binding of the repressor prevents RNA polymerase from attaching to the promoter and transcribing the genes of the operon -on-off switch is a segment of DNA -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
piwi-interacting RNAs (piRNAs)
-induces formation of heterochromatin, blocking expression of some parasitic DNA elements in the genome known as transposons -usually 24-31 nucleotides in length -are processed from a longer, single-stranded RNA precursor -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
epigenetic inheritance
-inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence
Chromatin-modifying enzymes
-initial control of gene expression by making a region of DNA either more or less able to bind the transcription machinery
repressible operon
-its transcription is usually on but can be inhibited (repressed) when a specific small molecule binds allosterically to a regulatory protein -ex. trp operon
expression of a protein-coding gene
-measured by the amount of functional protein a cell makes, and much happens between the synthesis of the RNA transcript and the activity of the protein in the cell
positional information
-molecular cues that control pattern formation in an animal or plant embryonic structure by indicating a cell's location relative to the organism's body axes -these cues elicit a response by genes that regulate development -cues tell a cell its location relative to the body axes and to neighboring cells, and determine how the cell and its descendants will respond to future molecular signals
interactions between embryonic cells
-molecules that transmit these signals within the target cell are cell-surface receptors and other signaling pathway proteins -in general, the signal sends a cell down a specific developmental path by causing changes in its gene expression that lead to observable cellular changes -helps induce differentiation into the many specialized cell types making up a new organism
myoblasts
-muscle cells that develop from embryonic precursor cells and have the potential to develop into a number of cell types, including cartilage cells and fat cells -particular conditions then commit them to becoming muscle cells -eventually start to churn out large amounts of muscle-specific proteins and fuse to form mature, elongated, multinucleate skeletal muscle cells
eukaryotic polypeptides
-must be processed to yield functional protein molecules -ex. cleavage of the initial insulin polypeptide forms the active hormone or chemical modifications can make protein functional
coordinately controlled genes
-often clustered into an operon
Coordinate control of dispersed genes in a eukaryotic cell
-often occurs in response to chemical signals from outside the cell -genes with the same sets of control elements are activated by the same chemical signals
small interfering RNA (siRNA)
-one of multiple small, single-stranded RNA molecules generated by cellular machinery from a long, linear, double-stranded RNA molecule -associates with one or more proteins in a complex that can degrade or prevent translation of an mRNA with a complementary sequence -blocking of gene expression by this is called *RNA interference (RNAi)*, is used in the laboratory as a means of disabling specific genes to investigate their function
regulatory mechanisms
-operate at the various stages after transcription -these mechanisms allow a cell to rapidly fine-tune gene expression in response to environmental changes without altering its transcription patterns
histone chemical modifications
-play a direct role in the regulation of gene transcription -
mRNA molecules
-produced during transcription -lifespan in the cytoplasm is important in determining the pattern of protein synthesis in a cell -bacterial: typically are degraded by enzymes within a few minutes(why bacteria can change their patterns of protein synthesis so quickly in response to environmental changes) -multicellular eukaryotes: typically survive for hours, days, or even weeks -nucleotide sequences can affect how long this remains intact are often found in the untranslated region at the 3‵ end of the molecule -most important RNAs because they code for proteins needs revision
Genome sequencing
-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
protein-protein interactions
-protein-mediated bending of the DNA brings the bound activators into contact with a group of mediator proteins, which in turn interact with general transcription factors at the promoter -help assemble and position the initiation complex on the promoter -allow these two DNA regions to come together in a very specific fashion, in spite of the many nucleotide pairs between them
mediator proteins
-proteins that mediate the interaction between regulatory proteins and the transcription factors
repression
-recruitment of chromatin-modifying proteins, most common mechanism in eukaryotic cells
selective degradation
-regulates length of time each protein functions in the cell -to mark a protein for destruction, the cell commonly attaches molecules of a small protein called ubiquitin to the protein -giant protein complexes called proteasomes then recognize the ubiquitin tagged proteins and degrade them
small noncoding RNAs
-regulating mRNAs -can cause remodeling of chromatin structure -ex. The siRNA system in yeast interacts with other, larger noncoding RNAs and with chromatin-modifying enzymes to condense the centromere chromatin into heterochromatin(not yet known for mammalian cells)
CRP
-regulating the lac operon -helps regulate other operons that encode enzymes used in catabolic pathways
non-protein-coding RNAs (noncoding RNAs, or ncRNAs)
-regulation from this occurs at several points in the pathway of gene expression, including mRNA translation and chromatin modification -microRNA (miRNA) -small interfering RNA (siRNA)
transcription factors
-segments of noncoding DNA that serve as binding sites for the proteins -bind to the control elements and regulate transcription -control elements on the DNA and the ___________ that bind to them are critical to the precise regulation of gene expression seen in different cell types 2 TYPES -General ________- act at the promoter of all genes -Specific ________- that bind to control elements that may be close to or farther away from the promoter
CRISPR-Cas9 system
-small ncRNAs used by bacteria as a defense system
Differentiated cells
-specialists at making tissue-specific proteins -each is a long fiber containing many nuclei within a single plasma membrane
inducible enzymes
-synthesis is induced by a chemical signal -usually function in catabolic pathways, which break down a nutrient to simpler molecules -by producing the appropriate enzymes only when the nutrient is available, the cell avoids wasting energy and precursors making proteins that are not needed
histone acetylation
-the attachment of acetyl groups to certain amino acids of histone proteins -appears to promote transcription by opening up chromatin structure
operon not switched off permanently
-the binding of repressors to operators is reversible(alternates between two states: one with the repressor bound and one without the repressor bound. The relative duration of the repressor-bound state is higher when more active repressor molecules are present) -repressor is an allosteric protein, with two alternative shapes: active and inactive, synthesized in the inactive form, which has little affinity for the operator (Only when a tryptophan molecule binds to the trp repressor at an allosteric site does the repressor protein change to the active form that can attach to the operator, turning the operon off)
pattern formation
-the development of a multicellular organism's spatial organization, the arrangement of organs and tissues in their characteristic places in three-dimensional space -begins in the early embryo, when the major axes of an animal are established -in a bilaterally symmetrical animal, the relative positions of head and tail, right and left sides, and back and front—the three major body axes—are set up before the organs appear
morphogenesis
-the development of the form of an organism and its structures -each has a particular mix of specific transcription factor activators that turn on the collection of genes whose products are required in the cell
differential gene expression
-the expression of different sets of genes by cells with the same genome
DNA methylation
-the presence of methyl groups on the DNA bases (usually cytosine) of plants, animals, and fungi (The term also refers to the process of adding methyl groups to DNA bases.) -occurs in most plants, animals, and fungi -long stretches of inactive DNA, such as that of inactivated mammalian X chromosomes, are generally more methylated than regions of actively transcribed DNA -DNA of individual genes is usually more heavily methylated in cells in which those genes are not expressed -removal of the extra methyl groups can turn on some of these genes -permanently regulates expression of either the maternal or paternal allele of particular genes at the start of development
Differentiation
-the process by which a cell attains its determined fate -1st sign: appearance of mRNAs for tissue-specific proteins -later, observable with a microscope as changes in cellular structure: different sets of genes are sequentially expressed in a regulated manner as new cells arise when their precursors divide
differentiation
-the process by which a cell or group of cells becomes specialized in structure and function -not randomly distributed but are organized into tissues and organs in a particular three-dimensional arrangement
determination
-the progressive restriction of developmental potential in which the possible fate of each cell becomes more limited as an embryo develops -at the end, a cell is committed to its fate -an embryonic cell can be experimentally placed in another location in the embryo and it will still differentiate into the cell type that is its normal fate
epigenetics
-the study of the inheritance of traits transmitted by mechanisms that do not involve the nucleotide sequence
gene expression
-typical human cell might express about a third to a half of its protein-coding genes at any given time -highly differentiated cells, such as muscle or nerve cells, express a smaller fraction of their genes -commonly controlled at transcription; regulation at this stage often occurs in response to signals coming from outside the cell, such as hormones or other signaling molecules -often equated with transcription for both bacteria and eukaryotes, not necessarily the case for eukaryotes -RNA-based regulation of chromatin structure plays in an important role of this
co-expressed eukaryotic genes
-typically scattered over different chromosomes -coordinate gene expression depends on every gene of a dispersed group having a specific combination of control elements, transcription activators in the nucleus that recognize the control elements bind to them, promoting simultaneous transcription of the genes, no matter where they are in the genome
inducible operon
-usually off but can be stimulated (induced) to be on when a specific small molecule interacts with a different regulatory protein -ex. lac operon
*Which of the following are required for the process of transcription?* A.transcription factors and amino acids B.RNA polymerase and the promoter C.DNA and DNA polymerase D.tRNA and RNA polymerase
B.RNA polymerase and the promoter
*How is euchromatin different from heterochromatin?* A.Heterochromatin is accessible to the enzymes responsible for transcribing genes, while euchromatin is not. B.Heterochromatin is the more densely arranged chromatin that is found during mitosis and meiosis, while euchromatin is the more loosely arranged chromatin found throughout the nucleus in interphase. C.Both consist of the 10-nm fiber, which during interphase is more densely arranged in euchromatin, and more loosely arranged in heterochromatin. D.Both consist of the 10-nm fiber, which during interphase is more densely arranged in heterochromatin, and more loosely arranged in euchromatin.
D.Both consist of the 10-nm fiber, which during interphase is more densely arranged in heterochromatin, and more loosely arranged in euchromatin.
*When a neuron responds to a particular neurotransmitter molecule by opening gated ion channels, the neurotransmitter molecules are serving as which part of the signal pathway?* A.transducing, or relay, molecule B.signaling receptor C.response molecule D.signaling molecule
D.signaling molecule
secondary transcription factors
activate the genes for proteins such as myosin and actin that confer the unique properties of skeletal muscle cells
Cytoplasmic determinants and inductive signals
contribute to spatially organizing the tissues and organs of an organism in their characteristic places, or pattern formation
genes are coordinately controlled
grouping genes of related function into one transcription unit allows a single "on-off switch" can control the whole cluster of functionally related genes
chromatin structure and gene expression
influenced by chemical modifications of both the histone proteins of the nucleosomes around which DNA is wrapped and the nucleotides that make up that DNA
addition of methyl groups to histones
lead to the condensation of chromatin and reduced transcription
RNA polymerase II
proceeds to transcribe the gene, synthesizing a primary RNA transcript (pre-mRNA)
master regulatory genes
protein products commit the cells to becoming skeletal muscle cells
promoter
site where RNA polymerase can bind to DNA and begin transcription
E. coli cell can sense the glucose concentration and relay this information to the lac operon
the mechanism depends on the interaction of an allosteric regulatory protein with a small organic molecule, cyclic AMP (cAMP) in this case, which accumulates when glucose is scarce -the regulatory protein, called cAMP receptor protein (CRP), is an activator, a protein that binds to DNA and stimulates transcription of a gene(CRP is also called catabolite activator protein, or CAP.) -when cAMP binds to this regulatory protein, CRP assumes its 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 lac promoter, which is actually rather low even when no lac repressor is bound to the operator -by facilitating the binding of RNA polymerase to the promoter and thereby increasing the rate of transcription of the lac operon, the attachment of CRP to the promoter directly stimulates gene expression -this mechanism qualifies as positive regulation.
Genes within heterochromatin
usually not expressed
Genes within euchromatin
whether or not a gene is transcribed is affected by the location of nucleosomes along a gene's promoter and also the sites where the DNA attaches to the protein scaffolding of the chromosome