Term
| instead of responding to the presence of molecules such as glucose or lactose in the external environment, cells in a multicellular eukaryote respond to _________ |
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Definition
| the presence of signals from other cells – from an internal environment |
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Term
| differential gene expression |
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Definition
| responsible for creating different cell types, arranging them into tissues, and coordinating their activity to form an individual |
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Term
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Definition
| DNA wrapped around proteins |
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Term
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Definition
| steps required to produce a mature, processed mRNA from a primary RNA transcript |
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Term
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Definition
| preliminary result of transcription |
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Term
| like bacteria, eukaryotes can control gene expression at __________ and at two additional levels of control: ________ |
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Definition
| transcription, translation and post-translation; chromatin and RNA processing |
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Term
| additional level of gene control in eukaryotes: chromatin |
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Definition
| eukaryotes have promoters, like bacteria; before transcription starts, DNA near promoter must be released from tight interactions with proteins so RNA polymerase can make contact with promoter; chromatin remodeling must occur prior to translation |
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Term
| additional level of gene control in eukaryotes: RNA processing |
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Definition
| sometimes, carefully orchestrated alterations of splicing of introns occur; when splicing events in primary RNA transcript change, different message emerges; altered message leads to different product |
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Term
| 6 potential control points in eukaryotic cell |
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Definition
| (1) chromatin remodeling (2) transcription initiation (3) RNA processing (4) mRNA stability (5) translation (6) post-translational modification of proteins |
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Term
| DNA packed in nucleus so tightly RNA polymerase can't access it b/c of ________ |
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Definition
| supercoiling; supercoiled DNA in bacteria doesn’t need to be altered extensively, but eukaryotic DNA has to undergo series of significant changes before transcription |
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Term
| Which of the following is most critical for the association between histones and DNA? |
|
Definition
| histones are positively charged |
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Term
| he primary difference between an enhancer and a promoter-proximal element is that ______ |
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Definition
| enhancers are at considerable distances from the promoter and can be moved or inverted and still function; promoter-proximal elements are close to the promoter and their position and orientation must be maintained |
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Term
| The TATA-binding protein (TBP) binds to _______ |
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Definition
|
|
Term
| The reason for differences in the sets of proteins expressed in a nerve and a pancreatic cell of the same individual is that nerve and pancreatic cells contain different _____ |
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Definition
| sets of regulatory proteins |
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Term
| _______ bind to DNA enhancer regions |
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Definition
| activators (type of transcription factor that bind to enhancer regions) |
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|
Term
| The bending of the DNA allows for the interaction of _________ |
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Definition
| transcription factors and RNA polymerase |
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Term
| Both _____ and _____ bind with the promoter |
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Definition
| RNA polymerase; transcription factors |
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Term
| An example of a basal transcription factor is ____ |
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Definition
|
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Term
| Regulatory transcription factors ______ |
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Definition
| influence the assembly of the basal transcription complex |
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Term
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Definition
| enzyme complexes that break down protein |
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Term
| The nuclear membrane's role in the regulation of gene expression involves _______ |
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Definition
| regulating the transport of mRNA to the cytoplasm |
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Term
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Definition
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|
Term
| Protein-phosphorylating enzymes' role in the regulation of gene expression involves _____ |
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Definition
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|
Term
| Alternative splicing takes place in the ________ |
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Definition
|
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Term
| The association of DNA with nucleosomes means that the default state for eukaryotic genes is to be ______ |
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Definition
|
|
Term
| Imagine you've isolated a yeast mutant that contains histones resistant to acetylation. What phenotype do you predict for this mutant? |
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Definition
| low levels of gene expression |
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Term
|
Definition
| most abundant DNA-associated proteins; intimately associated with DNA b/c DNA is negatively charge (phosphate groups) and histones are positively charge (lysine and/or arginine residues) |
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Term
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Definition
| "beads" on chromatin string; consists of DNA wrapped almost twice around a core of eight histone proteins; has a linker stretch of DNA between each pair |
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Term
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Definition
| histone that seals DNA to each set of 8 nucleosomal histones; interact with each other and with histones in other nucleosomes to produce a tightly packed structure (30-nanometer fiber), which are packed into still larger structures |
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Term
|
Definition
| made of chromatin that has several layers of organization - DNA wrapped around nucleosomes, nucleosomes packed into 30-nm fibers, 30-nm fibers folded into a structure still being studied |
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Term
|
Definition
| cuts DNA at random locations; cannot cut DNA efficiently if molecule is tightly complexed with histones |
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Term
| chromatin-remodeling complexes |
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Definition
| reshape chromatin through a series of reactions that are dependent on ATP |
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Term
|
Definition
| proteins create chromatin-remodeling complexes - associated with positive control (activation of genes) |
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Term
|
Definition
| proteins work by adding small molecules such as acetyl (CH3COOH) or methyl groups to histones; can be associated with either activation or inactivation - depends on which histones are altered and where methyl groups are on protein |
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Term
| histone acetyl transferases (HATs) |
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Definition
| enzymes that modify chromatin through acetylation or methylation; HATs acetylate positively charged lysine residues in histones; when a HAT adds an acetyl group to selected histones, number of positive charges on histones is reduced; result – less electrostatic attraction between histones and DNA; association between nucleosomes and DNA loosened, chromatin decondenses; on switch for transcription |
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|
Term
| histone deactylases (HDACs) |
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Definition
| enzymes that recondense chromatin; remove acetyl groups added by HATs; reverse effects of acetylation; off switch for transcription |
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Term
|
Definition
| patterns of inheritance that are not due to differences in gene sequences; muscle cells are different from brain cells in part because they inherited different types of modified histones – not different types of genes |
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|
Term
| chromatin must be _______ for RNA polymerase to bind to promoter |
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Definition
|
|
Term
| ________ first step in control of eukaryotic gene expression |
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Definition
|
|
Term
| two major types of proteins involved in modifying chromatin structure |
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Definition
|
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Term
|
Definition
| site in DNA where RNA polymerase binds to initiate transcription; eukaryotic promoters similar to bacterial promoters; most eukaryotic promoters just upstream of where RNA polymerase begins transcription; all have highly conserved element analogous to -35 box and -10 box in bacterial promoters |
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Term
|
Definition
| specific base sequence where a sigma-like protein binds and allows enzyme to contact DNA; in many genes that are transcribed by RNA polymerase II |
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Term
| TATA-binding protein (TBP) |
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Definition
| protein that binds all eukaryotic promoters; remember bacteria promoters may vary in sequence and bind different types of sigma proteins; eukaryotic genes also have promoters that vary in sequence, but all eukaryotic promoters are bound by TBP |
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Term
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Definition
| sections of DNA that are involved in controlling the activity of genes, similar to CAP site and operators |
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Term
| eukaryotic regulatory proteins |
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Definition
| change gene activity when they bind to regulatory sites; analogous to E. coli’s CAP and repressor protein |
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Term
| promoter proximal elements |
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Definition
| sequences that are located close to the promoter and bind regulatory proteins; just upstream from promoter and gene’s start site; unlike promoter, have sequences that are unique to specific genes; furnish a mechanism for eukaryotes to exert precise control over transcription |
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Term
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Definition
| proteins that bind to specific sties on other molecules; in immune system, bind to viruses and bacteria and mark them for destruction |
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Term
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Definition
| regulatory element far from promoter; exist in all eukaryotes and are unique to eukaryotes; can be more than 100,000 bases away from promoter; can be located in introns or in untranscribed 5’ -> 3’ sequences flanking the gene; different enhancers associated with different genes; can work even if normal 5’ -> 3’ orientation flipped; can work even if moved to a new location in the vicinity of the gene, on same chromosome; when regulatory proteins bind to enhancers, transcription begins (positive control) |
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Term
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Definition
| regulatory sequence similar in structure to enhancer but opposite in function; when regulatory proteins bind to silencers, transcription stops (negative control) |
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Term
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Definition
| section of DNA that codes for the functional polypeptide or RNA molecule along with regulatory sequences required for expression |
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Term
| two broad classes of regulatory proteins interact with regulatory sequences at the start of transcription |
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Definition
| regulatory transcription factors & basal transcription factors |
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|
Term
| regulatory transcription factors |
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Definition
| proteins that bind to enhancers, silencers, or promoter-proximal elements; responsible for expression of particular genes in particular cell types and at particular stages of development |
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Term
| in multicellular species, different types of cells express different genes because _________ |
|
Definition
| they contain different regulatory proteins |
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|
Term
| regulatory proteins are produced in response to _______ |
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Definition
| signals that arrive from other cells early in embryonic development |
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Term
| basal transcription factors |
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Definition
| interact with promoter and are not restricted to particular cell types; must be present for transcription to occur, but don’t provide much regulation; example: TBP, common to all genes; others are specific to promoters recognized by RNA polymerase I, II or III |
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|
Term
|
Definition
| involved in starting transcription; don’t bind to DNA; link proteins involved in initiating transcription – regulatory transcription factors and basal transcription factors; helps explain how regulatory sites can be so far from the transcription start site |
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|
Term
| basal transcription complex |
|
Definition
| multi-protein machine formed when all of the basal transcription factors have assembled at the promoter in response to interactions with regulatory transcription factors and coactivators; begins being constructed when TBP binds to TATA box in promoter, then many other proteins assemble around DNA-bound TBP |
|
|
Term
| basal transcription complex |
|
Definition
| multi-protein machine formed when all of the basal transcription factors have assembled at the promoter in response to interactions with regulatory transcription factors and coactivators; begins being constructed when TBP binds to TATA box in promoter, then many other proteins assemble around DNA-bound TBP |
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Term
|
Definition
| when the same primary RNA transcript is spliced in different ways to produce different mature mRNAs and thus different proteins |
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|
Term
| RNA-induced silencing complex (RISC) |
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Definition
|
|
Term
|
Definition
| single-stranded RNA held by RISC |
|
|
Term
| assembly of basal transcription complex depends on interactions with _________ that are bound to _______. result is ________ |
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Definition
| regulatory transcription factors; enhancers, silencers, and promoter-proximal elements; large, multimolecular machine positioned at start site and able to start transcription |
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|
Term
| alternative splicing is controlled by ________ |
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Definition
| proteins that bind to mRNAs in the nucleus and interact with spliceosomes |
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Term
| mRNA stability associated with changes in _________ |
|
Definition
| length of its poly(A) tail |
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Term
|
Definition
| degradation of an mRNA molecule or inhibition of its translation following its binding by a short RNA (microRNA) whose sequence is complementary to a portion of the mRNA |
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Term
| RNA interference begins when _______ |
|
Definition
| RNA polymerase transcribes DNA sequences that code for small RNA hairpin |
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Term
| in RNA interference, hairpin formation occurs b/c |
|
Definition
| pairs of sequences within RNA transcript are complementary |
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|
Term
| if match between miRNA & mRNA is perfect, ________ |
|
Definition
| enzyme in RISC destroys the mRNA (tight binding by an miRNA is a kiss of death for the mRNA) |
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|
Term
| if match between miRNA & mRNA isn’t perfect, _____ |
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Definition
| mRNA not destroyed (instead, translation is inhibited) |
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|
Term
| miRNAs responsible for ______ |
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Definition
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|
Term
| RNA interference usually operates at level of mRNA, after RNA processing is complete, but independent of translation, but many of the small RNAs responsible for RNA interference ___________ |
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Definition
| disrupt translation directly |
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|
Term
| four primary differences in gene expression in bacteria vs. eukaryotes |
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Definition
| (1) packaging (2) alternative splicing (3) complexity (4) coordinated expression |
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Term
| primary difference (1) in gene expression in bacteria vs. eukaryotes |
|
Definition
| packaging: chromatin structure of eukaryotic DNA must be opened for TBP, basal transcription complex, and RNA polymerase to gain access to genes and initiate transcription; b/c eukaryotic DNA packaged so tightly, default state in eukaryotes is off; default state in bacteria, which lack histones, is on; chromatin structure provides a mechanism of negative control that doesn’t exist in bacteria |
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|
Term
| primary difference (2) in gene expression in bacteria vs. eukaryotes |
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Definition
| alternative splicing: prior to translation, primary transcripts in eukaryotes must be spliced, something that’s very rare in bacteria; one-to-one correspondence between number of genes and number of gene products in bacteria isn’t seen in eukaryotes; each eukaryotic gene might code for one to thousands of distinct products |
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|
Term
| primary difference (3) in gene expression in bacteria vs. eukaryotes |
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Definition
| complexity: transcriptional control much more complex in eukaryotes than in bacteria; function of sigma proteins in bacteria analogous to basal transcription complex in bacteria; function of CAP, repressor & other regulatory proteins analogous to role of regulatory transcription factors in eukaryotes; sheer number of eukaryotic proteins and complexity of interactions dwarfs those in bacteria |
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|
Term
| primary difference (4) in gene expression in bacteria vs. eukaryotes |
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Definition
| coordinated expression: in bacteria, genes are involved in same cellular response organized into operons by single promoter; operons rare in eukaryotes; in eukaryotes, genes that are physically scattered can be expressed at the same time b/c single set of regulatory transcription factors can trigger transcription of several genes; eukaryotes coordinate the expression of functionally related genes |
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Term
| signal transducers and activators of transcription (STATs) |
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Definition
| group of regulatory transcription factors; common in cytoplasm of white blood cells in mammals, where they reside as single polypeptide chains (are inactive in this form) |
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|
Term
| for cancer to become dangerous, two things must happen: _______ |
|
Definition
| (1) rapidly growing cells must metastasize, meaning that some cells leave to invade other tissues (2) must stimulate growth of blood vessels that supply them with nutrients |
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|
Term
| many cancers are associated with mutations in _________ |
|
Definition
| regulatory transcription factors |
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Term
|
Definition
| radiation or chemicals that induce mutation |
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Term
|
Definition
| genes that stop or slow cell cycle; their products prevent cell cycle from progressing unless specific signals say conditions are ok for mitosis and cell division; example: p53 |
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Term
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Definition
| allele that promotes cancer development |
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Term
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Definition
| gene that is most often defective in human cancers; codes for a regulatory transcription factor; transcription factor that serves as master brake on cell cycle; p53 activated after DNA damage occurs (activated protein binds to enhancers of genes that arrest the cell cycle; once these genes activated, cell has time to repair its DNA before continuing to grow and divide); when a cell’s DNA extensively damaged and can’t be repaired, p53 causes apoptosis (when mutations in p53 make protein product inactive, damaged cells are not shut down or killed – instead continuing to move through cell cycle, except now are likely to contain many mutations b/c of DNA damage) |
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|
Term
| link between p53 protein activity and cancer? |
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Definition
| UV radiation damages DNA; close correlation between DNA damage and amount of p53 in a cell |
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Term
|
Definition
| (“first-cancer-genes”) genes that encourage cell growth by triggering specific phase in cell cycle; • in normal cells, required to initiate each phase in the cell cycle (active only when conditions are appropriate for growth); • in cancerous cells, defects in regulation of proto-oncogenes causes them to stimulate growth all the time |
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|
Term
| ________ is first step in control of eukaryotic gene expression |
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Definition
|
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Term
|
Definition
| tested hypothesis that DNA of actively transcribed genes is in an open configuration; compared chromatin of β-globin and ovalbumin genes (β-globin transcribed at high levels & ovalbumin gene never transcribed); found DNase cut up β-globin much more readily than ovalbumin |
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Term
| • many yeast genes that are normally never transcribed are transcribed at high levels at all times in certain mutant cells, suggests that they lack ______ |
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Definition
|
|
Term
| state of the ______ is fundamental to determining whether transcription can occur |
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Definition
| histone proteins that are complexed with DNA |
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|
Term
| pattern of chemical modifications _____ from one cell type to another |
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Definition
|
|
Term
| daughter cells inherit patterns of _______ from parent cells |
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Definition
| gene expression (example of epigenetic inheritance) |
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Term
| Oshima & the study of galactose |
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Definition
when galactose absent, yeast cells make tiny amounts of enzymes needed to metabolize it; when galactose present, transcription of genes encoding those enzymes skyrockets; studied mutants unable to use galactose; hypothesized cells had a knock-out mutation that disabled a regulatory protein
- thought to exert positive control, like CAP, over five genes that coded for those enzymes; five genes appeared to be regulated together; called hypothesized regulatory protein GAL4 |
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|
Term
| regulatory protein has a ______, analogous to helix-turn-helix motif |
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Definition
| DNA-binding domain, which binds to a short stretch of DNA just upstream from promoter for five genes that GAL4 regulates; location & structure of this sequence comparable to those of CAP binding site in lac operon of E. coli |
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Term
| Tonegawa & antibody gene broken into many introns and exons |
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Definition
| when introns placed close to a gene, gene's transcription rate increased, suggesting intron has a regulatory sequence |
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Term
| Tonegawa & genes with missing introns |
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Definition
| • if regulatory sequence located inside intron as predicted, some of the modified genes would lack sequence and fail to transcribe antibody gene - which is what happened |
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|
Term
| importance of Tonegawa's discovery of intron regulation |
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Definition
| (1) regulatory sequence thousands of bases away from promoter (enhancer) (2) downstream instead of upstream from promoter |
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|
Term
| GAL4 and other regulatory proteins bind to ________ and interact directly with _________. this helps _______ but raises the question of how ______ |
|
Definition
| promoter-proximal elements; TBP or RNA polymerase; stabilize binding and promote transcription; a regulatory protein far from promoter can help initiate transcription |
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|
Term
| eukaryotic genes are turned on when _________ |
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Definition
| specific regulatory proteins bind to enhancers and promoter-proximal elements |
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|
Term
| eukaryotic genes are turn off when ______ |
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Definition
| regulatory proteins bind to silencers |
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|
Term
| _______ are what make a muscle cell a muscle cell and a bone cell a bone cell |
|
Definition
| distinctive regulatory proteins |
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|
Term
| introns spliced out of primary RNA transcripts in _____ |
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Definition
|
|
Term
| mRNA that results from splicing consists of _______ |
|
Definition
| sequences encoded by exons and protected by a 5’ cap and long poly(A) tail on 3’ end |
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|
Term
| during splicing, changes in ______ are possible because selected exons, as well as introns, may be removed |
|
Definition
|
|
Term
| because of alternative splicing, ________ |
|
Definition
| same primary RNA transcript can yield mature, process mRNAs with several different combinations of transcribed exons (polypeptides translated from those mature mRNAs will vary) |
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|
Term
| splicing provides opportunity for regulation of gene expression |
|
Definition
|
|
Term
| before _______ was understood, thought genome had 60,000-100,00 genes, but actually have less than 20,000 |
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Definition
|
|
Term
| lifespan of mRNA controlled by _______ that bind to complementary sequences in mRNA - once part of an mRNA becomes double-stranded in this way, RNA interference occurs |
|
Definition
| tiny, single-stranded RNA molecules |
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|
Term
| overall rate of translation may slow/stop in response to increase of temp (to avoid _____) or infection by a virus (to avoid ______) |
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Definition
| misfolding; manufacturing viral proteins |
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|
Term
| post-translational control must give up _________ in order have ________ |
|
Definition
|
|
Term
| _______ is common mechanism of post-translational control, esp. in signal transduction pathways; can also be modified by _______ |
|
Definition
| phosphorylation; folding or by enzymes that cleave off a portion of the molecule |
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|
Term
| mutations lead to cancer when they affect one of two classes of genes |
|
Definition
| (1) genes that stop or slow the cell cycle (2) genes that trigger cell growth and division by initiating specific phase in cell cycle |
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|
Term
| how transcription is initiated in eukaryotes |
|
Definition
| (1) binding of regulatory transcription factors to DNA, which recruit chromatin-remodeling complexes and HATs, resulting in chromatin remodeling (2) region of DNA exposed, including promoter (3) regulatory transcription factors recruit proteins of basal transcription complex to promoter, DNA loops out and away from promoter to make contact (4) basal transcription complex is formed and recruits RNA polymerase II to start transcription |
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