Regulation of Gene
Expression
Chapter 18 (18.1 & 18.2)
Gene Expression
O All cells contain the entire genome
O In theory, every cell could make every single protein
encoded in the genome
O
But that doesn’t happen!
e.g. Lymphocytes of immune system are the only
cells that make antibodies while red blood cells are
the only cells that make the oxygen transport protein
hemoglobin
O Or sometimes the environment will influence which
proteins are made and when
O
O The spatial (space) and temporal (time) select
transcription of certain genes is called gene
expression
Gene Expression
So how do different cells know which genes to use
and which genes to ignore?
O It’s a little complicated so let’s start with the
prokaryotes!
O
Regulation in Prokaryotes
Bacterial cells only make gene products
when they are needed
O Bacteria can use 2 methods to regulate
this production:
1. Feedback regulation of enzymes
2. Gene expression regulation by the operon
model
O
Regulation by Operons:
Enzyme Production
O
Basic idea: Clusters of functionally
related genes are under coordinated
control
O A single “on-off switch”
O The switch is a DNA segment called an
operator
O Usually found inside the promoter
O An operon is everything involved:
operator, promoter and genes the operon
controls
Regulation by Operons
O Operons can be switched off by proteins
called repressors
O Repressors prevent gene transcription by
binding to operators and blocking RNA
polymerase
O Repressors are gene products of separate
regulatory genes
O Repressors can be active or inactive
O Corepressors make repressors active so
they can turn operons off (allosteric
regulation)
Regulation by Operons
If repressor present and active:
No transcription
O No gene products made
O
If repressor absent or inactive:
O Transcription occurs
O Gene products made
Negative Gene Regulation
Operons can be repressible or inducible
O Repressible operons are usually ON
O
O
An active repressor can shut them off
O Inducible operons are usually OFF
Inducer molecule inactivates repressor and
therefore turns on operon
O Ex. lac operon is an inducible operon
O
Negative Gene Regulation
O
Repressible operons usually found in
anabolic pathways (i.e. Pathways that
make bigger molecules)
O When enough product made, operon turns off
O Inducible operons usually found in
catabolic pathways (i.e. Pathways that
break down molecules)
O
Presence of reactant molecule will turn on
operon when necessary
Example of Inducible Operon:
lac operon
O E.coli can metabolize both glucose or lactose as
energy sources but it prefers glucose
O If environmental glucose is low and lactose is
high, lac operon transcribes genes for enzymes
used to break down lactose
O 3 genes needed for lactose metabolism:
O lacZ gene codes for b-galactosidase: Breaks lactose into
glucose and galactose
O lacY gene codes for permease: Allows lactose into cell
O lacA gene codes for transacetylase: Unknown role
lac operon: If no lactose
O
Since the lac operon is inducible, it is
normally OFF when no lactose
O
O
Would be a waste to make enzymes to break
down lactose if no lactose available
lac operon normally switched off by ACTIVE
repressor which binds to operator
Repressor made by regulatory gene lacI
O Repressor prevents RNA polymerase from
transcribing operon’s genes (lacZ, lacY, lacA)
O
Regulatory
gene
Promoter
Operator
lacI
lacZ
No
RNA
made
3
5
RNA
polymerase
Active
repressor
(a) Lactose absent, repressor active, operon off
i.e. No genes transcribed for lactose metabolism
lac operon: Lactose present
O If lactose present, b-galactosidase breaks
down lactose into allolactose first
O Allolactose binds to repressor, making it
inactive
Inactive repressor can’t block RNA polymerase
so operon transcribes genes (lacZ, lacY, lacA)
O Allolactose acts as an inducer in this role
O
lac operon
lacI
lacZ
lacY
lacA
Permease
Transacetylase
RNA polymerase
3
5
b-Galactosidase
Allolactose
(inducer)
Inactive
repressor
(b) Lactose present, repressor inactive, operon on
i.e. Genes transcribed to metabolize lactose
Regulation by Inducible Operons
If lactose present:
Allolactose (inducer) made
O Inducer makes repressor INACTIVE
O Operon ON
O Genes for lactose metabolism transcribed
O
If lactose absent:
No allolactose (no inducer) made
O Repressor stays ACTIVE
O Operon stays OFF
O Genes for lactose metabolism NOT transcribed
O
Eukaryotic Gene Regulation
O Remember that all cells are genetically
identical
O Yet each typical human cell only expresses
20% of its genes on average at a given time
O How do cells have such differential gene
expression?
Eukaryotic Gene Regulation
O Remember that all cells are genetically
identical
O Yet each typical human cell only expresses
20% of its genes on average at a given time
O How do cells have such differential gene
expression?
O Lots of levels of eukaryotic gene expression
control, from transcription to translation and
beyond!
Summary of
stages of gene
expression in
eukaryotes
Signal
NUCLEUS
Chromatin
DNA
Chromatin modification:
DNA unpacking involving
histone acetylation and
DNA demethylation
Gene available
for transcription
Gene
Transcription
RNA
Exon
Primary transcript
Intron
RNA processing
Cap
Tail
mRNA in nucleus
Transport to cytoplasm
CYTOPLASM
mRNA in cytoplasm
Degradation
of mRNA
Translation
Polypeptide
Protein processing, such
as cleavage and
chemical modification
Degradation
of protein
Active protein
Transport to cellular
destination
Cellular function (such
as enzymatic activity,
structural support)
Regulation of Chromatin Structure
O Recall from Chapter 16 that eukaryotic DNA
is wrapped around histone proteins, forming
chromatin
O Chromatin does more than just compact
DNA to fit in nucleus
O Amount of wrapping can control whether or not
gene expression occurs
O Tight wrapping = reduced transcription
O Looser wrapping = more transcription
O Heterochromatin regions very tightly wrapped with
little transcription (telomere & centromere regions)
Regulation of Chromatin Structure
O Chemical modification to histones and DNA
can also influence gene expression
O Acetylation (adding acetyl groups, -COCH3) to
positively charged histone tails reduces
attraction to negatively charged DNA
O Acetylation loosens chromatin = more transcription
O Deacetylation (removing acetyl groups) = less
transcription
Acetylation of
Histones
Histone
tails (+ charged)
DNA
double
helix (- charged)
Nucleosome
(a) Positive tails attracted to negative DNA; Prevents transcription
Unacetylated histones
Acetylated histones
(b) Acetylation makes histones less positive so less attraction
to DNA; Permits transcription
DNA Methylation
O Methylation (adding methyl groups, -CH3) can occur
on DNA itself, usually to cytosine nucleotides
O In general, more methylation = less transcription
O i.e. Methylation turns genes “off”
O Ex. Inactivated genes on mammalian X chromosome
that becomes Barr body are heavily methylated
Remember those tortoise shell
cats?
DNA Methylation
O
Methylation patterns can be passed on from
cell to cell
O
O
Helps cells differentiate into cell types during
embryonic development
But methylation patterns can ALSO change,
thus altering gene expression
Epigenetics
O But wait a minute! That’s a big
deal!
O Think about this: You inherit your
gene sequence BUT the expression
of those genes could change over
time with DNA methylation
changes
Epigenetics
Inheritance of traits not involving the
nucleotide sequence is called
epigenetic inheritance
O Epigenetics has profound implications
for human health
O
Ex. Could explain why one identical twin has a
particular disease and one doesn’t
O Ex. Some cancers shown to have a connection to
epigenetic modification
O