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Gene Regulation
‹Reading: Campbell Biology
Chapter 18 Bacterial Genetics (pp. 337-341, not trp)
Chapter 19 Eukaryote Gene Control (pp. 351-358)
‹Learning Objectives:
¾Know why genes must be regulated
¾Describe the lactose (lac) operon as an
example of bacterial gene regulation
¾Compare and contrast
prokaryotic and eukaryotic
gene regulation
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Gene Expression DNA Î RNA Î Protein
A powerful amplification process
e.g., silk fibroin gene:
Copies per silk gland cell
1 gene
104 mRNA molecules
109 protein molecules
(in 4 days)
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Enzymes ~ 103 conv / sec
Gene Expression DNA Î RNA Î Protein
Differentiation requires control
‹All cells in an organism have the same genes
¾differentiation = different cellular activity
¾requires precise control
‹Control of cellular activity = control of gene
expression
¾operates at various stages in the process
» transcription, transcript stability, translation,
transport, protein stability, enzyme activity
¾most efficient to regulate early
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Gene Regulation
Why not delete the unnecessary genes?
‹DNA is for
¾(1) storage, (2) transmission, (3) expression
of genetic information
‹Expression of different genes is needed
¾at different developmental stages
¾if surroundings change
‹Regulation rarely involves loss of genes
or changes to DNA
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Regulating Transcription
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‹Each gene (or bacterial operon) has its
own promoter
‹Regulatory proteins promote or inhibit
binding of RNA polymerase to promoters
Regulating Transcription
e.g. the lac operon in Escherichia coli
‹E. coli is a bacterium that lives in the gut
‹It can use lactose (milk sugar) as food
» this requires enzymes to metabolize lactose
lactose
permease
β-galactosidase
E. coli
Lactose
Lactose
Glucose + Galactose
(in gut)
(in E. coli )
(Carbon & Energy Sources)
» these enzymes Ï x103 in 15 min after supply of
lactose (host drinking milk) ie ‘inducible enzymes’
Regulating Transcription
lac operon: coordinated control
‹The genes for lactose metabolism are:
» clustered together on the chromosome
» controlled by a single promoter
» transcribed as a single transcript
‹1 promoter + several coding regions (cistrons)
= an operon
‹Allows
coordinated
control
Regulating Transcription
lac operon: negative control by repressor protein
‹If lactose is absent, a regulatory protein
(repressor) blocks lac transcription
» by binding to an upstream ‘operator’ sequence
» blocking RNA polymerase
Transcriptional control:
the bacterium does not
waste energy making
mRNA or enzymes for
lactose metabolism in the
absence of lactose
Regulating Transcription
lac operon: effect of an inducer (derepressor)
‹If lactose is present, lac is transcribed
» a lactose isomer binds to the repressor protein
» the bound repressor protein changes shape
» in this shape, it can not bind to the operator
» RNA polymerase can now bind & transcribe
Regulating Transcription
lac operon: positive control by CRP + cAMP
‹ If glucose is abundant
¾lac activity is not needed
‹ CRP is a positive
regulatory protein
¾activated by cAMP
¾assists RNA pol binding
¾Ï transcription rate
‹ If glucose is abundant
¾cAMP is scarce
¾little transcription of lac
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Regulatory Proteins
Key participants in transcriptional control
‹Products of regulatory genes
‹Often allosteric (shape determines activity)
‹Recognize & bind specific DNA sequences
‹Exert negative or positive effects
‹Some genes are affected by multiple
regulatory proteins (true for lac operon)
‹Some regulatory proteins affect multiple
genes
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Eukaryotic Gene Regulation
More genes, greater complexity: enhancers
‹Similar in principle to prokaryotes
» but no operons
−
allows multiple functions per gene?
» coordination by shared regulatory elements
‹Often multiple positive regulators / gene
» multiple ‘enhancer’ sequences
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Eukaryotic Gene Regulation
More genes, greater complexity: enhancers
‹Multiple positive regulators / gene allows
¾Fine control by
cumulative effects
¾Combinatorial control
» more patterns from fewer regulatory proteins
−
e.g. developmental patterns
Eukaryotic Gene
Regulation
Greater complexity: control levels
‹ Transcriptional control
» early, efficient
» but slow (expression lag)
‹ Enzyme activation
» expensive (~ waste energy)
» but fast
‹ More intermediate
opportunities in eukaryotes
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» e.g. RNA processing & transport
Regulatory Mutants
‹Gene expression in the
wrong place profoundly
changes development
» e.g. antennae like eyes
» e.g. double flowers
‹From sequence changes
» in promoters / enhancers
» in regulatory proteins
‹Important determinants of
evolution (e.g., multigene families)
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