Level of Gene

Control

Transcription:
Intrinsic and Extrinsic
Factors.
 Transcription Factors
• Transcription factors (TF) are proteins
involved in transcribing RNA from DNA
• TFs function to bind both DNA and proteins
• General (Basal) TFs initiate the transcription
apparatus
• Regulatory TFs influence the rate of
transcription
 DNA-binding domains

• Proteins contain motifs within the DNA binding

domain
 The eukaryote core promoter

• General transcription factors recognise and

bind to core promoter.
– Starting with TFIID which includes a TATA binding
protein (TBP)
 The eukaryote core promoter

• Other general transcription factors recognise

and bind to core promoter.
– TFIIF associates with RNA Polymerase II and
together they join the complex
– Note the Mediator complex.
General transcription factors plus RNA Polymerase
form the BASAL TRANSCRIPTION APPARATUS.
 The eukaryote promoter
• General transcription
factors recognise and
bind to core promoter.
• RNA Polymerase II is
recruited and then
positioned over the
transcriptional start
site.
• Transcriptional activator
proteins bind to
regulatory promoter
General transcription factors plus RNA Polymerase
and increase the rate of
form the BASAL TRANSCRIPTION APPARATUS. transcription.
Initiation of Transcription is regulated
by General Transcription Factors and
Transcriptional Activator Proteins.
• Transcriptional
activator proteins
stimulate and
stabilise the basal
transcription
apparatus at the
core promoter.
NOTE: TAP +/- coactivator interacts with RNA polymerase II
via the Mediator protein
Promoters are regulated by unique
combinations of transcriptional
activator proteins

Regulatory promoters
contain different
combinations of
consensus sequences
therefore the TAPs
that regulate the
promoter are unique.
Assembly on the promoter

https://www.youtube.com/watch?v=OxJp1YQqqNo
A closer look at the complexity of a
promoter
 Concept Check

Most transcriptional activator proteins affect

transcription by interacting with _____.

a. The regulatory promoter

b. The basal transcription apparatus
c. DNA polymerase
d. Nucleosomes
e. Mediator
f. TATA box
 DNA Elements that Control
Transcription
• Basal transcription factors are proteins that
bind to specific sequences (elements) within
the promoter to facilitate RNA polymerase
binding.

• Regulatory transcription factors are proteins

that bind to elements called
enhancers/silencers that are located away
from the promoter and interact with the RNA
polymerase through the mediator complex.
 Enhancer/Silencer elements
• Enhancers and silencers act over relatively
large distances.

• The influence of an enhancer or silencer of

gene expression is independent of orientation.

• The effects of enhancers and silencers are

independent of position. They may be
upstream, downstream, or in an intron.
 Regulation of Transcription by
Enhancers
• Transcriptional activator proteins that bind to
enhancers influence the activity of basal
transcription factors and RNA polymerase.
• These proteins are brought into contact with
one another by the mediator complex.
 Tissue-Specific Enhancers of the
Drosophila yellow Gene
• Yellow protein is required to produce
black melanin
• Expressed in a patter that correlates
with distribution of melanin.

Fig 18.6 Snustad & Simmons

 Spatial expression

https://ib.bioninja.com.au/higher-level/topic-7-nucleic-acids/72-transcription-and-gene/gene-
expression.html
 Enhancers and Insulators
• Most enhancers are capable of stimulating any
promoter in their vicinity.
• Insulators (boundary elements) block the
effects of enhancers in a position dependent
manner.
• Specific proteins bind to insulators and play a
role in their blocking activity.
• Some insulators limit the spread of changes in
chromatin structure.
 Transcriptional Repressors
Transcriptional repressor proteins can inhibit
transcription.
– Bind to sequences in the regulatory promoter
– Or silencer elements.
1. Compete with TAP for binding sites
– Different from prokaryotes where repressors block the
polymerase
2. Prevent activator from contacting basal
transcription apparatus
3. Interferes with basal transcription apparatus
assembly
Vol 26 no 3 pg 111
 Response elements
• Response elements: short regulatory consensus
sequences found in promoters or enhancers
• Varying distances from the genes being
regulated
• Bound by transcription factors
• Same response element present at multiple
genes........... all activated by the same stimulus
• Multiple response elements allows the same
gene to be activated by different stimuli
 Induction of Transcriptional
Activity by Environmental and
Biological Factors

Eukaryotic gene expression can be

induced by environmental factors such as
heat and light, and by signaling molecules
such as hormones and growth factors.
 Induction of the Drosophila hsp70
Gene by Heat Shock
• Heat shock proteins
(hsp) help stabilise the
internal cellular
environment.

• The expression of hsp

is regulated at the
transcription level and
is induced by heat
stress.
Fig 18.3 Snustad & Simmons
 Light Induces Ribulose 1,5-
Bisphosphate Carboxylase in Plants
• Ribulose 1,5-bisphosphate
carboxylase (RBC) is a
photosynthetic enzyme in
green plants.

• RBC is not needed in the dark.

• RBC is induced upon exposure

to light.
 Regulation of Gene Expression by
Steroid Hormones

Fig 18.4 Snustad & Simmons

 Regulation of Gene Expression by
Peptide Hormones

Fig 18.5 Snustad & Simmons

Regulation of Gene Expression by
Peptide Hormones

https://www.youtube.com/watch?v=vi-zWoobt_Q
 Hormone Response Elements
• Hormone response elements (HREs) are
analogous to the heat-shock response
elements.
• HREs are specific DNA sequences located near
the genes they regulate that bind specific
proteins that act as transcription factors.
 Activation of Transcription by
Hormones

• A steroid hormone/receptor complex binds to the

HRE sequence to stimulate transcription.

• For peptide hormones, the receptor stays at the cell

membrane; the signal is conveyed through the
cytoplasm by other proteins, causing a transcription
factor to bind to a regulatory sequence near a gene.
 Enhancers – Spatial and Temporal
Regulation
• Used a lacZ
reporter under
control of lincRNA
promoter
– Blue with X-gal
• Can determine
expression profile
of transcription
factors
Lai et al., 2015, PLoS ONE 10(4) e0125522
No legs for snakes

A subset of Hox genes regulate

limb development, therefore it is
reasonable to expect that in
animals without limbs there are
changed Hox gene clusters
Fig 23.9 Gilbert
 Hox genes in Drosophila

For more on anterior-posterior polarity in drosophila embryos see:

https://www.ncbi.nlm.nih.gov/books/NBK10039/ (Developmental Biology 6th ed.
 You put your left leg in:

Head of a fly containing an antennapodia mutation that

causes legs to develop where antennae should be.
 I’ve got my eye on you
• Mammalian homologues of
eyeless exist and are
functionally equivalent

• Ectopic expression of mouse

eyeless homologue in
drosophila produces ectopic
eye formation

• Mutations in the human

homologue cause eye
defects called anridia

Figure 25.28 Snustad and Simmons

Principles of Genetics
 Summary
1 Hormone binds to HRE which attracts
coactivator with HAT domain
2 Open the DNA structure (by regulation of the
histone core)
3 Expose the promoter of a gene
4 Open the structure of the gene (for example,
the coding region through the acetylation of
the histone core)
5 Recruit the basal transcription complex
 Key Points
• Transcription of the hsp70 genes in response to increased
temperature is mediated by a heat-shock transcription
factor.
• Transcription of the gene for the photosynthetic enzyme
ribulose 1,5-bisphosphate carboxylase (RBC) is induced
by exposure to light.
• Steroid hormones and their receptor proteins form
complexes that act as transcription factors to regulate
the expression of specific genes.
• Peptide hormones interact with membrane-bound
receptor proteins to activate a signaling system that
regulates the expression of specific genes.
Level of Gene
Control

Post-Transcriptional
Regulation:
mRNA processing and
mRNA stability