Chapter 16 Control of Gene Expression
occurs at many levels:
transcription initiation and rate post-transcriptional control (modifications, stability) translation initiation and rate post-translational control (modifications, stability)
gene expression is often controlled by regulatory proteins binding to specific DNA sequences regulatory proteins gain access to the bases of DNA at the major groove regulatory proteins possess DNA-binding motifs
helix-turn-helix motif homeodomain motif zinc finger motif leucine zipper motif
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Prokaryotic Regulation
regulatory proteins bind to DNA to either block or stimulate transcription, depending on how they interact with RNA polymerase control of transcription initiation can be:
positive control: increases transcription when activators bind DNA negative control: reduces transcription when repressors bind to DNA regulatory regions called operators
prokaryotic cells often respond to their environment by changes in gene expression genes involved in the same metabolic pathway are organized in operons some operons are induced when the metabolic pathway is needed and repressed when the metabolic pathway is no longer needed
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The lac operon
contains genes for the use of lactose as an energy source regulatory regions of the operon include the CAP binding site, promoter, and the operator the coding region contains genes for 3 enzymes:
-galactosidase, permease, and transacetylase
The lac operon is negatively regulated by a repressor protein:
lac repressor binds to the operator to block transcription when there is no lactose present in the presence of lactose, an inducer molecule binds to the repressor protein repressor can no longer bind to operator transcription proceeds
in the presence of both glucose and lactose, bacterial cells prefer to use glucose glucose prevents induction of the lac operon binding of CAP cAMP complex to the CAP binding site is required for induction of the lac operon high glucose levels cause low cAMP levels high glucose low cAMP no induction
The trp operon is negatively regulated by the trp repressor
the operon is expressed when tryptophan is absent
binding of repressor to the operator requires tryptophan (a corepressor) trp repressor binds to the operator to block transcription when tryptophan levels are high
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Fig. 16.20 overview of major levels of eukaryotic gene regulation
Eukaryotic transcription regulation
controlling the expression of eukaryotic genes requires transcription factors general transcription factors are required for initiation
required for proper binding of RNA pol to the DNA
specific transcription factors increase transcription in certain cells or in response to signals
General transcription factors bind to the promoter region of the gene RNA polymerase II then binds to the promoter to begin transcription at the start site (+1)
Formation of the initiation complex: 1) TFIID binds to the TATA box 2) then TFIIE, TFIIF, TFIIA, TFIIB, TFIIH 3) then several transcriptionassociated factors (TAFs)
that together recruit RNA pol II to the core promoter
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Enhancers are DNA sequences to which specific transcription factors (activators) bind to increase the rate of transcription where are enhancers located?
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Coactivators and mediators are also required for the function of transcription factors
coactivators and mediators bind to transcription factors and bind to other parts of the transcription apparatus
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Eukaryotic Chromosome Structure
chromatin structure is directly related to the control of gene expression
nucleosomes block RNA pol II from gaining access to promoters clusters of methylated cytosine nucleotides bind to a protein that prevents activators from binding to DNA methylated histone proteins are associated with inactive regions of chromatin acetylation of histone proteins are associated with active regions of chromatin
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Post-transcriptional regulation Control of gene expression usually involves the control of transcription initiation, but gene expression can be controlled after transcription, with mechanisms such as:
RNA interference alternative splicing RNA editing mRNA degradation
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Alternative splicing
different splice sites are recognized in different tissue types the mature mRNAs in each tissue possess different exons, resulting in different polypeptide products from the same gene
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mRNA stability
mature mRNA molecules have various half-lives depending on the gene and the location (tissue) of expression the amount of polypeptide produced from a particular gene can be influenced by the half-life of the mRNA molecules example:
during S phase, histone mRNAs have T of 1 hour during rest of cell cycle, polyA+ tail is lost and histone mRNAs are degraded within minutes
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Post-translational regulation
modifications that affect activity proteins degradation
proteins to be degraded are tagged with ubiquitin occurs at the proteasome
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Bonus Topics
miRNA siRNA
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