Download TOPIC 16: REGULATION OF GENE EXPRESSION

TOPIC 16: REGULATION OF GENE EXPRESSION (lecture 25)
OBJECTIVES:
1. Understand the basic mechanisms of control of gene expression in prokaryotes
including concepts of operon, repression and induction.
2. Understand the basic features of the tryp and lac operons
3. Understand the basic mechanisms of control of the appearance of finctional proteins
in eurkaryotes (from gene expression to post-translational modifications)
4. Understand the roles of distal and proximal control elements, transcription factors,
activators and the promoter in the control of gene expression in eurkaryotes.
Human genome has 30,000-100,000 DIFFERENT structural genes yet at any given
point in time only a fraction of these genes are being actively transcribed. This varies
from cell type to cell type as well as physiological state. How is this accomplished?
When prokaryotes are placed in new environments (for instance, media containing new
metabolic substrates) they alter the suite of proteins produced to take into account the
new environment. How is this accomplished?
BACTERIAL SYSTEMS- Regulation of Gene Expression.
Figure 18.19- Control of tryptophan biosynthesis.
(a) when Trp is needed, genes controlling enzymes of Trp biosynthesis are turned “on”
(b) as Trp accumulates it starts to inhibit its further synthesis by (i) directly inhibiting the
first enzyme in its biosynthetic pathway and (ii) starting to reduce the rate of
transcription of the genes coding for the enzymes of Trp biosynthesis.
How is this latter process (point ii) accomplished?
Trp OPERON (Figure 18.20) operon (sequence of E. coli DNA) consists of
(a) regulatory gene (codes for a repressor protein)
(b) promoter region
(c) operator site (binds “active” repressor protein)
(d) structural genes for Trp biosynthetic pathway
No Trp present: RNA polymerase binds to promoter and structural genes are
expressed.
Trp present:
(a) Trp binds to repressor protein making it “active” (capable of binding to
operator)
(b) “active” repressor protein binds to operator
(c) genes turned off; RNA polymerase no longer capable of transcribing
structural genes (this is REPRESSION)
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Lac OPERON (Figure 18.21) operon consists of
(a) lacI gene which codes for a repressor protein
(b) promoter region
(c) operator site (binds “active” repressor protein)
(d) structural genes for lactose transport and metabolism
No lactose present: repressor binds to operator (no transcription); note that the
repressor protein is “active in the absence of lactose.
Lactose present:
(a) lactose binds to repressor protein
(b) this inactivates the repressor making it incapable of binding to the operator
(c) RNA polymerase is now capable of transcribing structural genes (this is
INDUCTION)
Trp represses the Trp operon (negative control) and lactose induces the lac operon
(positive control)
EUKARYOTIC SYSTEMS- regulation of gene expression and the amount/quality of the
protein products of gene expression.
Figure 19.7- Levels of control
(a) transcription
(b) RNA processing
(c) mRNA transport
(d) translation
(e) post-translational modifications of protein
(f) degradation of protein
Figure 19.8- Eukaryotic gene structure (we’re going to focus mostly on transcriptional
control)
(a) Enhancers or distal control elements- located large distances from the
protein coding portions of the gene (100 to 1,000 bp away)
(b) Proximal control elements- located near the promoter
(c) Promoter- begins with a TATA box; site of binding of RNA polymerase
(d) Transcription factors- DNA binding proteins which regulate transcription
(e) Activators- special class of transcription factors which bind to the enhancers
thereby initiating the activation of gene expression
Figure 19.9 – Activation of transcription
(a) binding of activators to enhancer sites
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(b) bending of DNA so that enhancer region is in close proximity to promoter
region
(c) protein binding domains on activators binding to certain transcription factors
forming a transcription initiation complex including RNA polymerase
(d) transcription begins
activator proteins- nature depends on the gene regulated; could be a hormone-hormone
receptor complex (such as estrogen)
Post-translational Control
1.
2.
3.
4.
alternative splicing (see Fig. 19.11)
regulation of mRNA degradation
controlling rate of translation
protein modification and degradation (see Fig. 19.12)
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