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Regulation of Gene Expression
Regulation of Gene Expression
• Prokaryotes– Constituitive Gene Expression (promoters)– Regulating Metabolism (promoters and operators)– Regulating Development (sigma switches)
• Eukaryotes– Regulating genes in multicellular organisms
Constituitive Gene Expression (promoters)
promoter coding sequence
Regulating Metabolism (promoters and operators)
promoter coding sequenceoperator
Metabolic signals and repressor activitythe regulatory protein is an allosteric protein
metabolic signal
molecule
DNAbinding
site
repressorprotein
gene off
gene ongene off
gene on
repressoractivated
repressordeactivated
repressordeactivated
repressoractivated
repressor activatedgenes OFF
repressor deactivatedgenes ON
repressor activatedgenes OFF
repressor deactivatedgenes ON
precursor molecules macromolecule
energy
energy
substrate
product
Synthetic Pathway
Degradative Pathway
Repressors & metabolic pathways
repression
induction
Many regulatory proteins are dimers and bind to palindromes
negative control positive control
The Tryptophan Operon:Negative control of a synthetic pathway
the lac operon
Negative ControlWhen activated by binding of the metabolic signal molecule,
the lac repressor binds to the operator, blocking RNA polymerase
Positive ControlcAMP is present when glucose is unavailable
cAMP binds to CAP protein, which then binds to the promoterbinding of the CAP-cAMP complex to the promoter, activates
it
Positive ControlcAMP is present when glucose is unavailable
cAMP binds to CAP protein, which then binds to the promoterbinding of the CAP-cAMP complex to the promoter, activates
it
The Lactose Operon:Control of a degredative pathway
Practice
Answers
Control of development:Sigma switching
RNA polymerase in bacteria
core enzyme
sigma
Sigma factors recognize promoters and disassociate when the RNA polymerase binds to the promoter, leaving the core
enzyme to make the transcript
RNA polymerase
Each sigma can find a certain promoter
RNA polymerases
1 2 3 4 5 6 7
Phage SPOI (in B. subtilis)
• 3 phases of gene expression
– Early phase
– Mid phase
– Late phase
• Each phase uses a different sigma, each recognizing a different promoter
• The genes of each phase all have the same kind of promoter, recognized by one of the sigma factors
• Early phase. Early genes have promoters recognized by the host’s RNA polymerase. gp28 is an early protein that acts as a sigma factor for the middle phase genes. gp28 has a higher affinity for the CORE’s binding site than it’s own sigma, thus displacing the host’s sigma and turning off the early genes and turning on the mid genes.
• Middle phase . Middle phase genes have promoters recognized by gp28. Gp33 and gp34 are middle proteins that act as a sigma factor for the late genes.
• Late phase
early transcripts
early proteins,including gp28host
sigma
late transcripts
late proteinsgp33-34 sigma
middle transcripts
middle proteins,including gp33, gp34gp28
sigma
Sigma Switching
Eukaryotes
Prokaryote versus Eukaryote Comparison
Step 1
promoter
Step 2
Prokaryotes
Step 1
promoter
Step 2
Eukaryotes
promotersigma
Transcription Factor(eukaryotic sigma)
Positive control in eukaryotes - gene enhancers
Gene activation in Eukaryotes: A different complicated initiation complex for each different context in which a gene is expressed