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Gene Regulation in Prokaryotes
The lac operon is also subject to positive regulation What happens if both glucose and
lactose are present? Involves catabolite repressor Represses genes for catabolism of other
sugars if glucose is present Mediated by cAMP and CAP
CAP: catabolite gene activator protein also CRP: cAMP receptor protein
Gene Regulation in Prokaryotes
The lac operon is also subject to positive regulation (cont): Mechanism:
[increase] cAMP and [decreased] glucose: allows CAP binding to DNA
Stimulates transcription of lac operon Lactose-metabolizing enzymes produced
[increased] glucose depresses [cAMP] Restricts expression of lac Supresses use of secondary sugars
Regulon: coordinates regulated operons (CAP and cAMP)
Gene Regulation in Prokaryotes
The ara operon is (+) and (-) regulated by a single protein E. coli arabinose operon
One protein exerts both + and – regulation Binding a signal molecule alters
conformation from repressor form Repressor binds one DNA regulatory site Activator, without signal molecules, binds
to another DNA sequence
Gene Regulation in Prokaryotes
The ara operon is (+) and (-) regulated by a single protein
Ara C : regulates its own synthesis Represses transcription of its gene Called Autoregulation
Effects of some regulatory DNA sequences can be exerted from a distance via DNA looping
Gene Regulation in Prokaryotes Transcription Attenuation: regulates
genes for a.a. biosynthesis Genes for amino acid synthesizing enzymes
are clustered in operons Operons expressed when [a.a.] are
inadequate Trp operon of E. coli:
5 genes for conversion of chorismate to tryptophan mRNA from trp operon has 3 min half-life When [trp] increases, trp binds to trp repressor Causes conformational change in repressor protein
that permits binding to the operator Trp operator overlaps promoter, binding repressor
blocks RNA polymerase A ‘self-regulation’ mechanism
Gene Regulation in Prokaryotes
Transcription Attenuation: regulates genes for a.a. biosynthesis (cont) Transcription attenuation is a second trp
regulating mechnism Uses translation termination site “leader” blocks transcription Halts transcription before operon; halts RNA –
polymerase Couples transcription to translation via leader
peptide Attenuation of transcripts increases as [trp]
increases due to sensitivity of leader peptide to [trp]
Gene Regulation in Prokaryotes
Transcription Attenuation: regulates genes for a.a. biosynthesis (cont):
Each a.a. biosynthetic operon uses a similar strategy
Induction of SOS response requires destruction of repressor
Gene Regulation in Prokaryotes
Induction of SOS response requires destruction of repressor
SOS response is induced if chromosome is damaged
An example of coordinated regulation of unlinked genes
Multiple unlinked genes repressed by Lex A protein
All genes induced simultaneously when DNA is damaged
Triggers lysis of repressor Mediated by Rec A protein Rec A only binds to single stranded DNA
Gene Regulation in Prokaryotes
Regulated Developmental Switch: bacteriophage
Objective is assembly of new viruses without cell destruction
Choices are lysis or lysogeny Lysis: results in destruction of infected cell Lysogenic cycle
Virus may inhabit host cell for generations Viral DNA inserts into host, replicates passively Phage in this state: Prophage Some trigger induction Virus enters lytic phase
Gene Regulation in Prokaryotes
Regulated Developmental Switch: bacteriophage lamda (cont):
Bacteriophage lambda has a complex regulatory circuit
Oversees ‘choice’ between pathways Involves many lambda proteins Two (N and Q) act as anti-terminators Modify host RNA polymerase to by-pass
termination sites Other proteins serve as promoters or activators
Gene Regulation in Prokaryotes
Some genes are regulated by genetic recombination
Occurs spontaneously in prokaryotes Called: Phase Variation Physically moves promoters relative to
genes regulated Mechanism used by some pathogens as
defense against host immune system E.g.:Salmonella
Gene Regulation in Eukaryotes
Mechanisms resemble those in prokaryotes Positive regulation more common Involves selective binding of proteins
to control sequences Effect is modulation of rate of
transcription initiation
Gene Regulation in Eukaryotes Eukaryotic promoter and enhancer
elements mediate expression of cell-specific genes
Cells contain factors that recognize promoters and enhancers in the genes they transcribe
Transcription is accompanied by changes in chromosomal structure Lampbrush chromosomes Chromosome “puffs”
Gene Regulation in Eukaryotes
Transcription activator proteins required for binding RNA polymerase Some have general function Others are specific:
TATA-binding protein at “TATA-box” Activators required because eukaryotic
RNA-polymerase lacks ability to bind promoters
Gene Regulation in Eukaryotes Complex regulatory problems seen in
development of multicellular animals Genes function temporally and spatially Must act in succession Must be highly coordinated
Most genes expressed early in development Genes must be turned “off”, “on” in cell to
facilitate function Regulation involves expression and location of
genes and their products in developing organisms