Regulation of Gene Expression

• All genes not expressed at all times• All genes not expressed in all cells• Regulation of gene expression is necessary to

ensure production of necessary products in correct cells at most appropriate times

• Gene expression is regulated at various stages in prokaryotes and eukaryotes, with various methods being used

Transcriptional Regulation• Mostly occurs at level of initiation in bacteria• Negative regulation: some protein products only

transcribed and translated in presence of inducers• Conserves unnecessary use of cellular energy to

produce RNAs and proteins• Multiple genes expressed as operon– Operator near transcription initiation site controls

transcription– Repressor binds to operator to block transcription– Inducer must be present to block repressor for

transcription to occur– Operator is cis-acting, repressor is trans-acting

7.7 Metabolism of lactose

7.9 Negative control of the lac operon

7.10 Positive control of the lac operon by glucose

Transcriptional Regulation

• More complex in eukaryotes • Controlled at initiation or elongation• Proteins bind regulatory sequences and

modulate RNA polymerase activity: repressors, enhancers, promoters

• Modifications of chromatin structure plays a role

• Cis-acting sequences regulate eukaryote expression

7.20 The SV40 enhancer

7.21 Action of enhancers (Part 1)

7.21 Action of enhancers (Part 2)

7.22 DNA looping

7.23 The immunoglobulin enhancer

7.32 Action of eukaryotic repressors

7.37 Regulation of transcription by miRNAs

7.39 DNA methylation

7.41 Maintenance of methylation patterns

Translational Regulation

• mRNA translation regulated in prokaryotes and eukaryotes in response to cell stress, nutrient availability, growth factor stimulation

• Accomplished by repressor proteins, noncoding microRNAs, controlled polyadenylation, initiation factor modulation

• mRNA localization used in eggs, embryos, nerve cells and moving fibroblasts, to allow protein production in specific locations at appropriate time

8.15 Polysomes

8.16 Translational regulation of ferritin

8.17 Translational repressor binding to 3’ untranslated sequences

8.18 Localization of mRNA in Xenopus oocytes

8.19 Regulation of translation by miRNAs

8.20 Regulation of translation by phosphorylation of eIF2 and eIF2B (Part 1)

8.20 Regulation of translation by phosphorylation of eIF2 and eIF2B (Part 2)

Protein Folding and Processing

• Polypeptide products must be folded into 3-D conformation to function

• Some protein products consist of multiple polypeptide complexes

• Some proteins additionally modified by cleavage or attachment of other functional groups (carbohydrates and lipids)

8.21 Action of chaperones during translation

8.22 Action of chaperones during protein transport

8.23 Sequential actions of chaperones

8.27 Proteolytic processing of insulin

8.28 Linkage of carbohydrate side chains to glycoproteins

8.34 Palmitoylation

Protein Regulation

• Regulation of enzyme activity necessary for proper catalysis of biological reactions

• Accomplished through gene expression by regulating protein production, or regulation of protein function and activity in the cell

• Allosteric binding, phosphorylation, protein degradation used to regulate enzymatic function

8.36 Feedback inhibition

8.38 Protein kinases and phosphatases

8.39 Regulation of glycogen breakdown by protein phosphorylation

8.42 The ubiquitin-proteasome pathway

8.43 Cyclin degradation during the cell cycle

8.44 Autophagy

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