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Regulation of Transcri

ption Factors
The action of transcription factors can either
stimulate or inhibit gene expression.
They must be regulated so that a gene is expressed
only when its product is needed.
The following are a few examples.
Regulation of lac Repressor
The lac operon of E. coli consists of three
genes:- lacZ, lacY, and lacA, encoding -
galactosidase, lactose permease and
thiogalactoside transacetylase, respectively.
Lactose permease is located on the cell membrane,
capable of pumping lactose into the cell.
-galactosidase can convert lactose into glucose
and galactose .
Thiogalactoside transacetylase is responsible for
degrading small molecules.
In the absence of lactose, transcription of
the lac operon is inhibited by the lac repressor .
The lactose can bind to the lac repressor,
preventing it from interacting with its DNA
binding site.
Hence, in a medium containing lactose,
the lac operon is quickly transcribed, producing
the enzymes to generate glucose, which is the
major energy source for E. coli.
Regulation of Repressor (cI)

The life cycle of phages is controlled by cI and


Cro proteins.
The phage will remain in the lysogenic state if cI
proteins predominate, but will be transformed into
the lytic cycle if Cro proteins predominate.
Transcription of the two proteins is regulated by
the cI protein ( repressor) itself.
Regulation of the expression of cI and Cro proteins
by cI.
The cI dimer may bind to any of three operators,
OR1, OR2, and OR3, in the order OR1 > OR2 > OR3.
Binding of a cI dimer to OR1 enhances binding of a
second cI dimer to OR2.
Thus, OR1 and OR2 are almost always
simultaneously occupied by cI.
However, this does not increase the affinity
between cI and OR3, which will be occupied only
when the cI concentration is high.
(a) In the absence of cI proteins, the cro gene may
be transcribed.
(b) In the presence of cI proteins, only the cI gene
may be transcribed.
(c) At high concentration of cI, transcriptions of
both genes are repressed.
When the host DNA is damaged (e.g., under UV
irradiation), the cI protein may be cleaved by
certain protease promoted by the RecA protein.
Cleaved cI proteins cannot bind to the operators.
Thus, the Cro proteins can be produced to
transform the phage into the lytic cycle.
Regulation of NF-B

Nuclear factor-B (NF-B) is a ubiquitous


transcription factor that controls the expression of
genes involved in immune responses, apoptosis,
and cell cycle.
Incorrect regulation of NF-B may cause
inflammatory and autoimmune diseases, viral
infection and cancer.
Five mammalian NF-B family members have
been identified:-
1. NF-B1 (also called p50).
2. NF-B2 (also named p52).
3. RelA (also known as p65).
4. RelB.
5. c-Rel.
.They all share a highly conserved Rel homology
domain, responsible for their dimerization and
binding to DNA and IB (inhibitor of NF-B).
The transcription factor NF-B works only when
two members form a dimer.
The most abundant activated form consists of a
p50 or p52 subunit and a p65 subunit.
NF-B can be activated by a variety of stimuli,
including cytokines (such as TNF- and IL-1), T
and B cell mitogens, viral proteins, and stress
inducers (such as reactive oxygen species or UV
radiation).
In the cytoplasm, NF-B is inhibited by IB.
Upstream activating signal (e.g.,
binding of TNF- to its receptor) may cause
phosphorylation of IB by IKK (IB kinase).
This triggers the degradation of IB through
the ubiquitin system, where the target molecule
is masked by a chain of ubiquitins for degradation
by the 26S protesome.
The free NF-B can then translocate to the nucleus
and activate transcription.