Gene expression DNA RNA Protein
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Chapter 7: Gene control
Control of gene expression is critical in mediating cellular changes:
•Executing developmental programs•Controlling cell cycle•Responsiveness to regulators
There are many examples of evolutionary variation in promoters and transcriptional regulators
Since all cells in an organism have the same DNA, how do the cells become different?
(1) Some genes are expressed only in specific tissues (e.g., hemoglobin)
Since all cells in an organism have the same DNA, how do the cells become different?
(2) Genes expressed in all cells are termed housekeeping genes:• cytoskeleton building blocks• metabolism• histones, polymerases
Since all cells in an organism have the same DNA, how do the cells become different?
(3) Even housekeeping genes are expressed at different levels-metabolic profiles of red and white muscle
Since all cells in an organism have the same DNA, how do the cells become different?
(4) Post-transcriptional processes (Fig 7-5) also critical in regulating function:-mRNA processing-mRNA transport and localization-mRNA degradation-translation-post-translational modification-3-dimensional organization-compartmentation-protein degradation
Fig 7-5. Gene expression is controlled at many levels
Cells can change expression in response to external signals
Many cells use hormonal signals to trigger changes in gene expression:
e.g., glucocorticoids induce changes in metabolic enzyme expression in liver
Cells can change expression in response to external signals
Different cells respond differently to the same hormones:
e.g., glucocorticoids in liver: induction of genes that enhance conversion of amino acids to glucose.
-in adipocytes, glucocorticoids repress the same gene
Transcriptional control
Genes are regulated by promoters (regions upstream of coding region)
Genes can also be regulated at sites that are distant from promoters (even in introns)
Gene regulatory proteins
Regulatory regions of DNA have short sequences (elements) that bind specific gene regulatory proteins
e.g., Sp1 binds GGGCGGCCCGCC
These proteins recognize subtle differences in the structure of the outside of the major groove of the DNA double helix
Gene regulatory proteins
Each protein differs in how it binds DNA and how it interacts with other proteins
Several common DNA binding motifs including:
-helix-turn-helix motif (Fig 7-14), include homeodomain proteins
-zinc finger proteins (Figs 7-17-19)
-leucine zippers (Fig. 7-21)
-helix-loop-helix (HLH) (Fig 7-25)
Gene regulatory proteins
DNA binding ability of gene regulatory proteins can be influenced by:
-localization
-dimerization (homodimers vs heterodimers)
Tryptophan repressor is a simple model of ligand-dependent gene regulation
(Fig-7-34, 7-35)
Repressor protein can bind DNA and trp
If trp absent, repressor cannot bind DNA (un-repressed)
When trp available, repressor binds and prevents RNA Pol from binding gene
Eukaryotic gene expressionWhat regulates transcription (Fig 7-41)
Promoter: binding site for RNA Pol II and general transcription factors
Other regulatory sequences can be far away (even 50,000 bp)
Activators (or enhancers) bind to specific DNA sequences (modify local DNA structure)
Eukaryotic gene expression
Gene activators
Activators can work synergistically (Fig 7-47)
Order of binding of activators and combination of activators influences transcription (Fig 7-48)
Gene repressors
Repressors can work many different ways (Fig 7-49)
-competition with activators for sites
-masking activation site on activator
-disruption of general transcription factors
-affecting chromatin remodelling
Co-activators and co-repressors
These proteins do not bind DNA but bind DNA-binding proteins (Fig 7-50)
Myogenesis: an example of programmed transcriptional regulation (Fig 7-72)
Precursor cells are myoblasts
Hormonal conditions cause differentiation: turning on suites of muscle-specific genes in the appropriate order
Hormones induce expression of myogenic factors (transcription factors)
Control of gene expression1. Localization of transcription factors
Xkinase
kinase
Hormone
Control of gene expression2. Dimerization
kinase
kinase
Hormone
Control of gene expression3. Affinity for DNA (phosphorylation dependent)
kinase
kinase
Hormone
Control of gene expression4. Affinity for DNA (ligand dependent)
Hormone
Control of gene expression5. Affinity for DNA (ligand dependent)
Hormone
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