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expression
Sadava: 16.3
16 3 Regulation of eukaryotic genes;
16.4 Epigenetic changes; 16.5 Regulation
after transcription
Eukaryotic Transcription
Eukaryotic genes are encoded by exons interspersed
by introns.
In Eukaryotes,the
Eukaryotes the primary transcript is processed by
adding a 5cap, a 3polyA sequence and removal of
introns ((byy splicing).
p
g)
In Eukaryotes, more than 1 protein product can be
made by 1 eukaryotic gene through a process of
alternative
lt
ti splicing
li i off exons.
In addition to the promoter site(s) there are enhancer
sites (far
( far upstream) for activators to bind; regulation
by repressors and activators is more complex than in
prokaryotes
Gene expression
G
i can be
b
regulated at several points
in the transcription and
translation processes
processes.
E.g., expression of genes
must be precisely
regulated during
development.
Figure 16.13 Potential Points for the Regulation of Gene Expression (Part 2)
In eukaryotes,
transcription factors
(regulatory proteins)
must assemble on the
chromosome before
RNA polymerase can
bind to the promoter.
TFIID binds to the TATA
box; then other
t
transcription
i ti ffactors
t
bind, forming a
transcription complex.
RNA polymerase
II one of the
polymerases in
eukaryotes
B, E, F, H =
other
transcription
factors, which
will
ill be
b different
diff
t
for different sets
of genes/cellular
purposes
Helix-turn-helix
Zinc finger
Leucine
zipper
Helix-loop-helix
Mental Health
20% of Canadians will
personally experience a
mental illness in their
lifetime.
Suicide accounts for
24% of all deaths among
15-24 year olds and 16%
among 25-44
25 44 year olds
olds.
10-20% of Canadian
youth are affected by a
mental illness or disorder
CMHA, 2013
Figure 16.13 Potential Points for the Regulation of Gene Expression (Part 1)
Chromatin remodeling:
DNA is wound around
histones to form
n cleosomes which
nucleosomes,
hich
block initiation and
elongation.
One remodeling protein
disaggregates the
nucleosome to allow
initiation (making
space for the
polymerase
complex).
The second remodeling
protein
p
ote b
binds
ds to tthe
e
nucleosomes to allow
elongation to
proceed.
Histone acetylation
Histone p
proteins have tails with p
positively
y charged
g amino
acidsenzymes add acetyl groups:
This reduces positive charges, and decreases affinity of
histones for negatively charged DNA.
Allows chromatin remodeling
Histone modifications
Not a histone
modification
DNA methylase
catalyses
y addition
of methyl groups to
C at CG (CpG)
sites; represses
transcription need
to remove
(demethylase) to
enable transcription
Epigenetic regulation in
depression (in rats/mice)
BDNF expression
is reduced in the
hippocampus
after social
defeat
Figure 16.13 Potential Points for the Regulation of Gene Expression (Part 2)
Figure 14.21 Alternative Splicing Results in Different Mature mRNAs and Proteins
Figure 16.13 Potential Points for the Regulation of Gene Expression (Part 3)
Micro RNAs
Mi
RNA (about
( b t 20
bases long) bind to
mRNA before it
reaches a ribosome.
ribosome
Causes the target mRNA
to break down, or
inhibits translation
translation.
A protein complex called
dicer cuts the parent
RNA strand
strand.
Small RNAs (siRNA) are
under development as
drugs to block gene
expression of certain
genes in human
diseases. [2006 Nobel
prize]
i ]
Figure 16.13 Potential Points for the Regulation of Gene Expression (Part 3)
Chapter summary
How Is Eukaryotic
y
Gene Transcription
p
Regulated?
g
Eukaryotic gene expression is regulated both during and after transcription. Review Figure 16.13, WEB
ACTIVITY 16.1
Transcription factors and other proteins bind to DNA and affect the rate of initiation of transcription at the
promoter. Review Figure 16.14 and Figure 16.15, ANIMATED TUTORIAL 16.3
The interactions of these proteins with DNA are highly specific and depend on protein domains and DNA
sequences.
Genes at distant locations from one another can be coordinately regulated by common transcription factors and
promoter elements. Review Figure 16.17
How Do Epigenetic Changes Regulate Gene Expression?
Epigenetics refers to changes in gene expression that do not involve changes in DNA sequences
sequences.
Modifications of histone proteins in nucleosomes make transcription either easier or more difficult. Review
Figure 16.19
DNA methylation can explain genome imprinting, where the expression of a gene depends on its parental origin.
Review Figure 16.20
How Is Eukaryotic Gene Expression Regulated After Transcription?
Alternative splicing of pre-mRNA can produce different proteins. Review Figure 16.22
MicroRNAs are small RNAs that do not code for proteins, but regulate the translation and longevity of mRNA.
Review Figure 16.23
The proteasome can break down proteins, thus affecting protein longevity. Review Figure 16.24. SEE WEB
ACTIVITY 16.2 for a concept review of this chapter.