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AP Bio- Information 12: Regulation of Gene Expression

12 of 12 of my Information Domain (2 Discussions) Credits:Biology (Campbell) 9th edition, copyright Pearson 2011, & The Internet. Provided under the terms of a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. By D. Knuffke.
by David Knuffke on 25 November 2014

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Transcript of AP Bio- Information 12: Regulation of Gene Expression

Regulation of Gene Expression
Prokaryotes
Eukaryotes
In prokaryotes, transcription and translation happen simultaneously (they are "coupled")

Prokaryotes regulate gene expression (and therefore their metabolism) almost entirely by regulating transcription.

The lack of a nucleus makes this very efficient.
Eukaryotes regulate gene expression (and therefore their metabolism) at every step of protein synthesis from pre-transcription to post-translation.
Refer to organized clusters of genes that all contribute to a particular metabolic task.

Prokaryotes only!!!

2 Major Flavors:
Inducible
and
Repressible
Operons:
Inducible:
Repressible:
"Up Regulation":
Precursor
Enzyme 1
Enzyme 2
Enzyme 3
-
-
Gene 1
Gene 2
Gene 3
Gene 4
Gene 5
Product
Inhibition of
enzyme activity
Inhibition of
transcription
Francois Jacob & Jacques Monod
Nobel Prize: 1965
For metabolic pathways that are usually "off".

Ex: The
Lac
Operon
(digests lactose)
For metabolic pathways that are usually "on".

Ex: The
Trp
Operon
(synthesizes tryptophan)
When Lactose is absent:
The repressor protein (made by the
LacI

gene) is able to attach to the
operator
(a region of the promoter)
RNA polymerase cannot transcribe the
structural genes
(
LacZ
,
LacY
and
LacA
) that the cell needs to be able to digest lactose, since it can not attach to the promoter.
This is how things remain in the cell as long as there is no lactose present.
When Lactose is present:
The
inducer
molecule (
allolactose
, a form of lactose) binds to the repressor protein.
This changes the shape of the repressor protein so that it can not attach to the promoter.
RNA polymerase is then able to transcribe the structural genes that the cell needs to be able to digest lactose.
This is how things remain in the cell until lactose is digested
What kind of feedback?
When tryptophan is absent:
The repressor protein (made by the
TrpR
gene) is unable to attach to the operator
RNA polymerase can transcribe the structural genes (
TrpE
,
TrpD
,
TrpC
,
TrpB
, &
TrpA
) that the cell needs to be able to synthesize tryptophan.
This is how things remain in the cell as long as there is no tryptophan present.
When Tryptohan is present:
The
corepressor
molecule (
tryptophan
) binds to the repressor protein.
This changes the shape of the repressor protein so that it can attach to the promoter.
RNA polymerase can not transcribe the structural genes that the cell uses to synthesize tryptophan.
This is how things remain in the cell until tryptophan is no longer present.
What kind of feedback?
A way to increase the rate of transcription of an operon

Ex: The
CAP/cAMP
System
When Lactose is present and glucose is low:
Low glucose means the amount of
cyclic AMP
(
cAMP
) is high
cAMP binds to the
Catabolite Activator Protein
(
CAP
), activating it
The Activated
cAMP/CAP complex
increases the rate of transcription of the lac operon (and ~100 other catabolic operons), boosting the rate of transcription several fold.
When Glucose and Lactose are both present:
Normal glucose level means the amount of cyclic AMP (cAMP) is low
cAMP is not bound to CAP
CAP is inactive.
Very little lac structural gene transcription occurs.
What kind of feedback?
What kind of logic?
What kind of logic?
What kind of logic?
Levels of Control
1.DNA Access
2.Pre-Transcription
3.Post-Transcription
Recent research has uncovered many forms of "
non-coding" RNA
(
ncRNA
) molecules in cells.







We'll look at one example, active in regulation of gene expression post-transcription and pre-tranlstion
4.Pre-Translation
5.Post-Translation
The
decoupling of

Transcription
&
Translation

allows for
more control
points

Only keep necessary genes accessible.
In eukaryotes, DNA is "wound" around
histone
proteins.

The addition of
acetyl

groups
(
-CH2CH3
) to histones causes them to become less tightly packed, allowing for access to the DNA.

Heterochromatin
: more tightly packed DNA, unavailable for transcription.

Euchromatin
: less tightly packed DNA, available for transcription.

Cool fact: Histone acetylation patterns seems to be heritable. Epigenetics strikes again!
Recent research shows that even in interphase, the "loose" chromosomes occupy distinct nuclear regions.

"
Transcription factories
": Areas of the nucleus where active regions of different chromosomes interface. May be associated with common functions

Thousands of transcription factories in any nucleus
All the actors need to be present for the play to begin.
Eukaryotic genes interact with many "upstream" regulatory elements. These are DNA sequences that preceede a transcription unit that need to have specific proteins present for RNA polymerase to begin transcription.
The proteins that mediate RNA Polymerase are known as "
Transcription Factors
":
Control of transcription factor availability is one of the major ways that cells of a multicellular organism accomplish "
differential gene expression
", which in turn allows cells to "
differentiate
" to serve different functions in the organism.

This is crucial!!!
So many options lead to so many outcomes.
Following transcription,
5' capping
and
3' poly-adenylation
are necessary for eukaryotic mRNA to remain functional and be transported to the cytoplasm for translation.
"
Alternative splicing
" of exons allows for multiple functional (or non-functional) gene products to be made from a single primary transcript.

Anywhere from 75 - 100 percent of human genes with multiple exons probably undergo alternative splicing.

Shown here: the
Troponin T
gene produces 2 different mRNA sequences to produce 2 different gene products.

Not shown: A Drosophila gene that has enough exons to produce 19,000 different transcripts.
Lots still left to learn
RNA Interference (
RNAi
):
Mediated by a group of tiny RNA molecules ("
Micro RNA
" or
miRNA
).

The miRNAs are produced after the transcript for them is cleaved into multiple fragments by a "
dicer
" protein.

The miRNAs complex with proteins.

Any mRNA with a sequence complementary to an miRNA is "tagged" with the miRNA/protein complex.

Tagged miRNA molecules are not translated.

Nobel Prize: 2006
Don't let unnecessary proteins hang around.
Ubiquitin
(a protein so plentiful in all eukaryotic cells it is "ubiquitous"), will tag unnecessary proteins for transport to a proteasome. Inside the
proteasome
, the protein is broken down.
Nobel Prize: 2004
Proteasomes are abundant in eukaryotic cells (why?)
Big Question
Make sure you can:
Polyribosomes demonstrating the coupling of transcription and translation in prokaryotes:
Prokaryotic control of metabolism through control of transcription:
Wikipedias "list of RNAs"
(Oct. 2011):
Coding RNAs
How is gene expression controlled?
Explain the structure and function of all expression control systems described in this presentation.

Compare and contrast the expression control systems utilized in prokaryotic and eukaryotic cells.

Relate prokaryotic expression control systems to prokaryotic cellular organization and feedback mechanisms.

Relate eukaryotic expression control systems to eukaryotic cellular organization and the decoupling of transcription and translation.
RNAi
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