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Gene regulation
biology 1 lecture 13
• Differential expression of genetic code
in prokaryotes and eukaryotes
• Regulation at the transcription level
• How DNA is read - regulatory proteins
• Motifs
• Control by polymerase blocking in
prokaryotes
• Control ‘at a distance’ in eukaryotes
• Post-transcriptional control
Gene expression is controlled by
regulating transcription
• Regulation of promoter access
• Transcriptional control in prokaryotes is more
straight forward
• Bacteria configure expression of genes to fit
environment; generally reversible
– RNA polymerase must bind to promoter
– Protein regulators bind to promoter to either
• Inhibit binding of RNA polymerase
• Facilitate binding of RNA polymerase
Regulatory proteins read DNA
without unwinding it
• Regulatory proteins bind to major
groove of DNA helix, reading base pairs
outside edge
• Several motifs are seen that bind to the
DNA molecule
– Helix-turn-helix
• Homeodomain
– Zinc-finger
– Leucine zipper
Prokaryotes limit transcription by
blocking the polymerase
• Repressors are off-switches
– e.g., tryptophan producing [trp] genes in
E.coli: block of trp operon at promoter
prevents transcription of 5 genes related to
enzymes needed to make tryptophan
– Presence of tryptophan shuts down
transcription
• Activators are on-switches
– e.g, catabolite activator protein (cap) of
E.coli.
– Decrease of glucose leads to increase in
cAMP
– cAMP binds to CAP, protein changes
shape
– CAP's helix-turn-helix motif binds to DNA
near several promoters
– Promoters activates, genes transcribed
Switches combine to form complex
control systems
•
•
e.g., the lac operon of E.coli produces three proteins that import
disaccharide lactose,breaking it into two monosaccharides, glucose
and galactose
The activator switch
– lac operon has two regulatory sites
• CAP site adjacent to lac promoter
– Ensures genes not transcribed when glucose is present
– If glucose absent, high levels of cAMP in cell
• cAMP binds to CAP,CAP binds to DNA, promoter functional
– If glucose present, levels of cAMP are low
• CAP prevented from binding to DNA, lac promoter not functional
•
The repressor switch
– Operator is second regulatory site, adjacent to promoter fig 16.12
– lac repressor binds to operator, only when lactose absent
– Repressor covers part of promoter when bound to operator
•
Result: lac operon only expressed when glucose not present, and
lactose present
Transcription control in eukaryotes is
more complex
• Cells prefer constant conditions - gene
expression help control homeostasis
• Changes in gene expression produce
variety of results
– Compensate for changes in body's
physiological condition
– Ensure that correct genes are expressed in
development
• Changes in gene expression serve
needs of whole, not individual cell
Control ‘at a distance’
• Eukaryotes make use of transcription factors,
complex multi-protein molecules that cause DNA to
loop.
• Therefore, blocking of regulatory proteins at some
distance down a DNA sequence may effect a gene’s
expression - may involve ‘enhancers’
• Binding of transcription factor begins at, but is not
limited to, the TATA box
• Transcription inhibited by
– Anything that reduces availability of any factor
– Anything that limits its ease of assembly into complex
• In vertebrates, methylation may be involved
Post-transcriptional control
• Gene splicing removes introns
• Possible control of transport of mRNA
out of nucleus
• Translation repressor proteins (prevent
binding of ribosome)
• Selectively degrading mRNA transcripts
(e.g., growth factor transcripts are
notoriously unstable)