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Transcript
Gene Regulation, Part 1
Lecture 15
Fall 2008
1
Metabolic Control in Bacteria
• Regulate enzymes
already present
– Feedback Inhibition
– Fast response
• Control production of
enzymes
– Regulates transcription
– Longer-term response
Fig. 18.2
2
Metabolic Control in Bacteria
• Operon
– Unit of genetic function, found in bacteria and
phages, consisting of an operator, promoter &
coordinately regulated cluster of genes whose
products function in a common pathway
3
Metabolic Control in Bacteria
• Promoter
– Specific area of DNA that designates the start of a
gene
– Where RNA polymerase binds
• Operator
– Sequence of nucleotides near the start of an operon
to which an active repressor can attach
– On-off “switch” for the cluster of genes
Fig. 18.3
4
Metabolic Control in Bacteria
• Regulatory gene
– Gene that codes for a protein that controls the
transcription of another gene or group of genes
• Repressor
– Protein that inhibits gene transcription
– Binds to operator & prevents RNA polymerase from
attaching to promoter
Fig. 18.3
Metabolic Control in Bacteria
• Repressors
– Specific to an operator of a specific gene
• Regulatory genes expressed continuously, but
at low rate
– On-off regulated by concentration of
repressors
– Repressors are allosteric proteins
• Active & inactive form
• Corepressors
– Small molecules that cooperate with repressor to turn off
transcription
5
6
Metabolic Control in Bacteria
• Repressible Operon
– Operon where transcription is normally “on”,
but that can be inhibited (repressed)
– E.g., trp operon (tryptophan)
Fig. 18.3
Metabolic Control in Bacteria
trp operon
• trp repressor synthesized in an inactive form
• Tryptophan acts as corepressor
Fig. 18.3
7
8
Metabolic Control in Bacteria
• Inducible operon
– Operon where transcription is normally “off”, but that
can be stimulated (induced)
– E.g., lac operon (lactose)
• lac repressor
synthesized in
active form
• Binds to operator
• Prevents RNA
Polymerase from
binding
Fig. 18.4
Metabolic Control in Bacteria
• Inducer binds to lac repressor
• Inducer: specific small molecule that binds to repressor
protein and changes its shape
– Repressor inactivated
– Releases/does not bind with operator
– Transcription occurs
Fig. 18.4
9
Negative and positive gene regulation
• Negative gene regulation
– Operons switched off by active form of a
repressor protein
– E.g., lac and trp operons
• Positive gene regulation
– Regulatory protein interacts directly with the
genome to switch transcript on
10
11
Negative and positive gene regulation
Lactose metabolism only occurs when glucose
concentrations low
• Catabolite activator protein (CAP) & cyclic AMP (cAMP)
• CAP is activator
– Protein that binds to DNA and stimulates transcription of a gene
• cAMP concentration high when glucose concentration low
• cAMP activates CAP
Fig. 18.5
Negative and positive gene regulation
• CAP attaches to CAPbinding site on promoter
• Increases affinity of RNA
polymerase for promoter
• Activators increase the rate
of transcription
– As long as lactose is
present, transcription
can still occur
Fig. 18.5
12