Topic 4 Simple Organic Chemistry

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Unit 3 Molecular Biology GENE CONTROL
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GENES ARE REGULATED Different genes are expressed
at different times to control early
development. Different genes are expressed in
different cell, tissue, and organ types to give
them their unique functions. Different genes are
expressed in response to different environmental
conditions.
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Bacteria as model for studying the regulation of
transcription
Metabolism genes involved in metabolic
reactions are regulated in response to nutrients
lactose turns on transcription of genes for
enzymes in pathway - genes are INDUCIBLE
tryptophan turns off transcription of genes for
enzymes in pathway Genes are REPRESSIBLE
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The Lac Operon
RNA polymerase
lac z
lac y
lac a
promoter
lac z codes for b-galactosidase (breaks lactose
into glucose and galactose) lac y codes for
permease (transports lactose into cell) lac a
transacetylase (function not clear)
promoter DNA sequence bound by RNA polymerase
needed for transcription
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Repressor always expressed from lac I gene. It
binds to DNA sequence of operator, prevents
binding of RNA polymerase to promoter. Operon
off. Example of negative control factor that
modulates transcription (repressor) has negative
effect.
Some of lactose converted to allolactose and this
binds to repressor. This binding causes repressor
to change its shape, can no longer bind to
operator. RNA polymerase CAN bind to promoter and
transcribe operon. Operon is INDUCIBLE, and
allolactose is the INDUCER.
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lactose turns on transcription of genes for
enzymes in pathway - genes are INDUCIBLE
tryptophan turns off transcription of genes for
enzymes in pathway Genes are REPRESSIBLE
The trp operon, a repressible gene system.
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The way the operon is set up is very similar to
the lac operon. The important difference is that
the repressor is inactive when first made,
meaning that it cannot bind to the trp operator
on its own. In the absence of other signals, RNA
polymerase binds to operator, operon is
transcribed . . .
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. . . But when tryptophan is present at
sufficient levels, some of tryptophan binds to
repressor, turning it into an active repressor
that can bind to operator and shut down
transcription.
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The previous examples both were negative control
the molecule that affected transcription
(repressors) had inhibitory effects on
transcription. It is also possible to have
POSITIVE control, where the regulator enhances
transcription. The mechanism is usually simple
the RNA polymerase binds weakly to the promoter
on its own, but a transcription factor bound to a
nearby enhancer sequence interacts with the RNA
polymerase to help it bind more strongly to the
promoter.
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Even in presence of lactose, expression of the
lac operon is dependent on a positive regulator.
Efficient binding of RNA polymerase to the
promoter requires interaction with a complex
between cyclic AMP (cAMP) and the CAP protein.
This cAMP/CAP complex is a positive regulator.
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Purpose of this additional control?
cAMP levels vary in response to GLUCOSE. When
glucose is not available, cAMP levels are high,
lac operon expressed.
In this manner cells monitors for GLUCOSE as well
as for lactose, and GLUCOSE is the preferred
substrate. So if glucose is available, shut off
this (and other) sugar related operon.
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These mechanisms just described for controlling
transcription in E. coli are common in
prokaryotic organisms.
In eukaryotes, the separation of transcription
and translation into different cell
compartments, and the existence of several
mechanisms of mRNA modification, provide more
steps for modulating gene expression.
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A widely used mechanism for controlling
eukaryotic gene expression is to control the
localized condensation (folding) of the chromatin.
Methylation of DNA bases promotes condensation
while acetylation of histone proteins promotes
the unwinding of DNA and expression of genes.
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The transcription process itself is also used to
regulate gene expression in eukaryotes.
Hormones are substances that are transported
through the blood or lymph from a cell where they
are produced to another cell where they affect
gene expression. Testosterone is produced in the
testes of human males. It is picked up by other
cells in the body that express a testosterone
receptor, and the testosterone/testosterone
receptor complex is a positive transcription
factor that turns on male specific genes.
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Another common mechanism to modify gene
expression is called alternative mRNA splicing.
Using this mechanism, the introns and exons in a
single mRNA can be spliced in different patterns
to produce from several to several thousand
different mature mRNAs that each code for
slightly different proteins.
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And theres more . . .