Transcript Ch. 18 Eukaryotic Gene Expression notes

Ch. 18 Regulation of Gene
Expression
Objectives:
LO 3.18 The student is able to describe the connection between the regulation of gene expression and
observed differences between different kinds of organisms.
LO 3.19 The student is able to describe the connection between the regulation of gene expression and
observed differences between individuals in a population.
LO 3.20 The student is able to explain how the regulation of gene expression is essential for the
processes and structures that support efficient cell function.
LO 3.21 The student can use representations to describe how gene regulation influences cell products
and function.
LO 3.22 The student is able to explain how signal pathways mediate gene expression, including how this
process can affect protein production..
LO 3.23 The student can use representations to describe mechanisms of the regulation of gene
expression.
18.1 Bacteria Often Respond to Environmental
Change by Regulating Transcription
Conserve resources 1 of 2 ways:
• Feedback inhibition (discussed in Ch. 8)
• Regulation of gene expression (discussed here)
Precursor
Feedback
inhibition
trpE gene
Enzyme 1
trpD gene
Enzyme 2
Regulation
of gene
expression
trpC gene

trpB gene

Enzyme 3
trpA gene
Tryptophan
(a) Regulation of enzyme
activity
(b) Regulation of enzyme
production
Operons: The Basic Concept and Negative Gene
Regulation
Operons:
• Operator (“on/off switch”), promoter, and genes.
– Repressible (anabolic) operons: Always “on” until repressor is bound.
(inhibited)
• Corepressor is like feedback inhibition (product works with repressor)
• Ex: tryptophan producing genes
trp operon
Promoter
DNA
Regulatory
gene
mRNA
Promoter
Genes of operon
trpD
trpC
trpE
trpR
3
RNA
polymerase
Operator
Start codon
mRNA 5
5
Inactive
repressor
(a) Tryptophan absent, repressor inactive, operon on
D
No RNA
made
mRNA
Tryptophan
(corepressor)
(b) Tryptophan present, repressor active, operon off
C
B
A
Polypeptide subunits that make up
enzymes for tryptophan synthesis
DNA
Protein
trpA
Stop codon
E
Protein
trpB
Active
repressor
• Inducible (catabolic) operons are usually off but can be
induced.
– Inducer inactivates the repressor
– Ex: lac (lactose) operon
Regulatory
gene
DNA
Promoter
Operator
lacI
lacZ
No
RNA
made
3
mRNA
RNA
polymerase
5
Active
repressor
Protein
(a) Lactose absent, repressor active, operon off
lac operon
lacI
DNA
lacZ
lacY
lacA
RNA polymerase
3
mRNA
5
mRNA 5
-Galactosidase
Protein
Allolactose
(inducer)
Inactive
repressor
(b) Lactose present, repressor inactive, operon on
Permease
Transacetylase
Positive Gene Regulation
• Gene is always on but activator stimulates
transcription.
– Ex: cAMP
Promoter
Promoter
DNA
lacI
CAP-binding site
lacZ
Operator
RNA
polymerase less
likely to bind
Inactive
CAP
Inactive lac
repressor
(b) Lactose present, glucose present (cAMP level low):
little lac mRNA synthesized
DNA
lacI
lacZ
CAP-binding site
Active
CAP
cAMP
Operator
RNA
polymerase
binds and
transcribes
Inactive lac
repressor
Inactive
CAP
Allolactose
(a) Lactose present, glucose scarce (cAMP level high):
abundant lac mRNA synthesized
18.2 Eukaryotic Gene Expression is
Regulated at Many Stages
Signal
NUCLEUS
Chromatin
• Each cell of multicellular
organisms contain all
genetic info; only some is
expressed (differential
gene expression).
– Each process has the
potential for regulation.
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
Histone
tails
DNA
double
helix
Amino acids
available
for chemical
modification
Nucleosome
(end view)
(a) Histone tails protrude outward from a nucleosome
Unacetylated histones
Acetylated histones
(b) Acetylation of histone tails promotes loose chromatin
structure that permits transcription
• Histone Modifications:
acetylation loosens
chromatin  easier
protein access.
• DNA Methylation:
addition of methyl group
to gene turns it off.
• Epigenetic Inheritance:
gene regulation passed
on to offspring.
Regulation of Transcription Initiation
• Control elements/enhancers upstream from a
gene can activate or repress transcription
factors to regulate gene expression.
• Combination of control elements and their
activators.
– Like genes use similar control elements and
activators.
Mechanisms of Post-Transcriptional Regulation
• mRNA degradation
• Alternative RNA splicing: different
intron/exons spliced together.
Exons
DNA
1
3
2
4
5
4
5
Troponin T gene
Primary
RNA
transcript
3
2
1
RNA splicing
mRNA
1
2
3
5
or
1
2
4
5
Animation: Blocking Translation
Right-click slide / select “Play”
© 2011 Pearson Education, Inc.
Animation: Protein Processing
Right-click slide / select “Play”
© 2011 Pearson Education, Inc.
18.3 Noncoding RNAs Play Multiple Roles in
Controlling Gene Expression
• Parts of DNA that make very small RNA (ncRNA) but not
proteins; regulate gene expression.
– Bind to a complementary sequence of mRNA, blocking translation.
– Bind to DNA changing chromatin structure
1. microRNAs (miRNA): begins as hairpin
2. Small interfering RNAs (siRNA): begins as double strand
Hairpin
Hydrogen
bond
miRNA
Dicer
5 3
(a) Primary miRNA transcript
miRNA
miRNAprotein
complex
mRNA degraded
Translation blocked
(b) Generation and function of miRNAs
18.4 A Program of Differential Gene Expression Leads
to the Different Cell Types in a Multicellular Organism
• Embryonic development:
division  differentiation
 morphogenesis
Cytoplasmic Determinants
• RNA and proteins from
mom’s cell unevenly
distributed giving rise to
different cells during 1st
divisions.
(a) Cytoplasmic determinants in the egg
Unfertilized egg
Sperm
Fertilization
Zygote
(fertilized egg)
Mitotic
cell division
Two-celled
embryo
Nucleus
Molecules of two
different cytoplasmic
determinants
Induction is how embryonic
cells effect one another due
to cell-surface molecules or
growth factors.
(b) Induction by nearby cells
Early embryo
(32 cells)
Determination due to the
expression of genes for
tissue-specific proteins.
NUCLEUS
Pattern Formation puts
determined cells in their
“proper places” for the
resulting organism.
Signal
transduction
pathway
Morphogens (proteins)
establish an embryo’s axes
Signaling
molecule
(inducer)
Signal
receptor
Animation: Development of Head-Tail Axis in Fruit Flies
Right-click slide / select “Play”
© 2011 Pearson Education, Inc.