Alberts • Bray • Hopkin • Johnson • Lewis • Raff • Roberts • Walter
Essential
Cell Biology
FOURTH EDITION
Chapter 8
Control of Gene Expression
Copyright © Garland Science 2014
The vast differences in size
and morphology of different
cell types is due to
differences in gene
expression from the same
genome.
Fig. 8-1
β cells of pancreas: insulin
α cells of pancreas: glucagon
B cells: antibodies
RBC: hemoglobin
skeletal muscle: muscle actin
and myosin
neuron: neurotransmitters/
receptors
liver: gluconeogenesis
enzymes, signaling proteins
Ability to deprogram terminally differentiated
cells shows that all cells of a multi-cellular
organism contain a full genome.
even
mammals!
Fig. 8-2
Gene expression can be controlled at many levels.
*
Fig. 8-3
Regulation at first step of primary importance
Transcription regulators bind specific DNA sequences
through interaction with the major groove.
Fig. 8-4
amino acids H bond
with nitrogenous bases
sequence-specific binding
Homeodomain: one class of DNA-binding domain
Our earliest knowledge of transcriptional
regulation came from studies in bacteria.
Bacteria have genes of related function transcribed from a single promoter.
Fig. 8-6
Transcriptional Repressor Allosterically Regulated
trans-acting factor
cis-acting sequence
product of genes activates the repressor when product present in medium
Fig. 8-7
Transcriptional Activator Also Allosterically Regulated
trans-acting factor
CAP
cAMP
cis-acting sequence
Example:CAP activator at Lactose operon activated by cAMP
when glucose (preferred C source) absent
Fig. 8-7
Lac operon: binding sites for both
an activator and a repressor
Genes encode enzymes
for lactose catabolism
cAMP (no glucose)
activates
lactose
inactivates
Activator
Repressor
inactive
inactive
inactive
active
active
active
active
inactive
Fig. 8-9
In eukaryotes, activators and repressors
can work from long distances (>100 kb)
trans
factor
cis
sequence
Mediator links enhancer to
preinitiation complex
through DNA bending
Fig. 8-10
Many activators act through altering chromatin.
Swi/SNF
HAT
ATP
Animation
Fig. 8-11
Either can make TATA box available to TBP.
(0:30)
Activators and Repressors Act By Committee:
Combinatorial Control
Fig. 8-12
Example of Combinatorial Control:
Drosophila Embryo
Each regulatory segment specifies particular stripe
Fig. 8-12
promoter-reporter gene fusion
made by recombinant DNA technology
Each regulatory segment provides binding
sites for a different set of regulatory proteins.
repressors high
stripe too broad when lacking these
activators high
Fig. 8-14
stripe too weak when lacking these
Repressors and activators expressed in precise spatial pattern and
temporal order during embryogenesis.
Specific combinations of regulatory proteins
induce specific cell fates from precursor cells.
Fig. 8-12
A single regulatory protein can induce a cell fate.
Introduction of neuron-specific regulators
into liver cell induces differentiation into neuron!
Fig. 8-16
Introduction of multiple Embryonic Stem (ES)
cell-specific regulators into fibroblast induces
de-differentiation into ES-like cell
(induced Pluripotent Stem cell)!
Fig. 8-18
have potential
for gene therapy
A single regulatory
protein can even
direct development
of entire organ
Ey regulator expression
in leg precursor results
in eye development in
Drosophila leg!
Fig. 8-19
Cells have memory mechanisms that allow
them to record a decision made after
ceasing expression of a regulatory protein
during early embryogenesis.
1) Feedback Loop
2) DNA methylation
3) Histone modification
Cell-Memory Mechanisms
Type 1) Feedback Loop
regulatory protein
regulates its own
transcription
Fig. 8-20
Type 2) DNA Methylation
(Cytosine of CG dinucleotide)
Fig. 8-21, 22
Heterochromatin Assembly Involves
Binding of HP1 to H3-MeK9
H3-MeK9
& HP1
HP1
Fig. 5-26
H3-MeK9 also
recruits enzyme
needed for similar
modifications
of replicated DNA
Type 3) Histone Modification
Fig. 8-23
histone modification enzyme
recruited by binding to its
own modification, providing
memory mechanism
Translational Control
Examples in Bacteria:
Ribosomal proteins inhibit their
own translation when in excess
Fig. 8-24
L. monocytogenes mRNA contains
thermosensing sequence
The genome sequencing projects and
studies in model organisms have revealed
the presence of many functional RNAs
that are non-coding (ncRNAs)
1) micro RNAs (miRNAs)
2) small interfering (siRNAs)
3) long non-coding RNAs (lncRNAs)
At least one third of human protein-coding
genes are regulated by miRNAs.
Fig. 8-25
RISC also targets dsRNAs from
foreign transpososon and viral DNA
In lower eukaryotes,
RISC also recruits
heterochromatin
proteins to silence
foreign DNA.
Fig. 8-2
Heterochromatin Assembly Involves
Binding of HP1 to H3-MeK9
H3-MeK9 enzyme
recruited to TEs
by RISC and
siRNA from TE
HP1
Fig. 5-26
H3-MeK9
& HP1
then H3-MeK9
provides memory
mechanism
Heterochromatin can also provide a heritable
inactive chromatin state to cellular genes
(as in X chromosome inactivation)
Random expression of
Xist long ncRNA from Xp
selects it for inactivation
Xm has equal chance
of being selected
random choice
remembered:
Pc & H3-MeK27
heterochromatin
proteins
Fig. 5-30
Clonal pattern of X inactivation responsible
for coat pattern of calico cats
Pc Complexes keep neuron-specific genes off
in liver cells and vice versa
Fig. 8-16
Neuron-specific regulators also remove facultative
heterochromatin of liver cell!