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Chapter 16 BIO 1510

Control of gene expression in prokaryotes and eukaryotes involves regulatory proteins binding to DNA and controlling transcription. In prokaryotes, genes are organized into operons which are regulated by repressors and activators in response to environmental conditions. In eukaryotes, transcription is controlled by general transcription factors, specific transcription factors like activators and coactivators, and epigenetic mechanisms such as DNA methylation and histone modification. Post-transcriptional gene expression is also regulated by mechanisms like alternative splicing, microRNAs, and protein modifications.

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73 views

Chapter 16 BIO 1510

Control of gene expression in prokaryotes and eukaryotes involves regulatory proteins binding to DNA and controlling transcription. In prokaryotes, genes are organized into operons which are regulated by repressors and activators in response to environmental conditions. In eukaryotes, transcription is controlled by general transcription factors, specific transcription factors like activators and coactivators, and epigenetic mechanisms such as DNA methylation and histone modification. Post-transcriptional gene expression is also regulated by mechanisms like alternative splicing, microRNAs, and protein modifications.

Uploaded by

Chachi C
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We take content rights seriously. If you suspect this is your content, claim it here.
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Control of Gene Expression

Chapter 16
Control of Gene Expression
• Prokaryotes regulate gene expression in response
to changes in the immediate environment (e.g.,
food supply)

- many changes are reversible

• Eukaryotes regulate gene expression to maintain


homeostasis (dynamic constancy of the internal
environment) throughout the whole organism, not
just within the individual cell

- many changes are irreversible


DNA-Binding Regulatory Proteins
• Gene expression is often controlled by regulatory
proteins binding to DNA

- regulatory proteins may block transcription by


getting in the way of RNA polymerase or
stimulate transcription by helping RNA
polymerase locate the promoter

- regulatory proteins bind to


specific DNA sequences in the
major grooves

- regulatory proteins possess


DNA-binding motifs
DNA-Binding Motifs

• Regions of regulatory proteins which bind to


DNA

- helix-turn-helix motif

• homeodomain motif

- zinc finger motif

- leucine zipper motif


The Helix-Turn-Helix Motif
• Two adjacent  helices separated by turn of several
amino acids

- one helix fits in the major groove and the other


lays against the outside of the DNA molecule
The Homeodomain Motif

• Special class of helix-turn-helix


motifs

• Found in proteins that bind to


genes expressed during specific
stages of development
The Zinc Finger Motif

• Uses zinc atoms to coordinate DNA binding

- the more zinc fingers in


the cluster, the stronger
the protein binds to the
DNA
The Leucine Zipper Motif

• Two leucine-rich regions interact with each other,


forming a zipper

- the regions beyond the zipper


form a Y-shaped structure
that grips the DNA in
scissor-like configuration
Prokaryotic Regulation
• Control of transcription initiation

– positive control increases frequency of


initiation

• activators enhance binding of RNA polymerase


to promoter

– negative control = decreases frequency of


initiation

• repressors bind to operators (regulatory


sites on DNA) to prevent or decrease the
Prokaryotic Regulation
• Many genes in bacteria are found in operons

- under control of same promoter and


transcribed together as one unit

- lactose (lac) operon

- tryptophan (trp) operon

• Induction – enzymes for a certain pathway are


produced in response to a substrate

• Repression – capable of making enzymes but do not


The lac Operon in E.coli

• Consists of a promoter, an operator, and three genes


(lacZ, lacY, and lacA), which encode three enzymes
that metabolize lactose
When Lactose is Absent…

• The lac operon is negatively regulated by a repressor


protein

- lac repressor binds to the operator to block


transcription
When Lactose is Present…

• An inducer molecule (allolactose) binds to the repressor


protein

• Repressor can no longer bind to operator

• RNA polymerase is allowed to move forward and start


transcription
When Glucose is Low and Lactose is Present…

• The lac operon is positively regulated by an activator, the


catabolite activator protein (CAP)

• cAMP binds to CAP, forming the CAP-cAMP complex that binds


to CAP-binding side of DNA and causes it to bend

• This bending makes RNA polymerase binding to the promoter


more efficient
When Glucose Levels are High and Lactose is Absent…

• cAMP levels decrease, the CAP–cAMP complex is not


formed, and RNA polymerase is blocked by the lac
repressor
What Happens when Glucose Levels are High
and Lactose is Present?
The trp Operon in E. coli
• Consists of five genes that encode five enzymes used to
manufacture tryptophan

• It is negatively regulated by the trp repressor protein

• When tryptophan is present, the trp repressor binds to


the operator and blocks transcription oftrp operon
The trp Operon in E. coli

• When tryptophan is absent, the cell needs to make


tryptophan

- repressor does not bind operator

- RNA polymerase is allowed to move forward and


start transcription
Eukaryotic Regulation
• Control of transcription is more complex

- more than one “ON”


and “OFF” switches
are needed around the
promoter

- some of the control switches


are therefore further away from
the promoter
Transcription Factors
• General transcription factors

- necessary for the assembly


of a transcription apparatus
and recruitment of RNA
polymerase II to a
promoter

- TFIID (binds to
to the TATA
box), TFIIE, TFIIF, TFIIA, TFIIB, and
TFIIH
Transcription Factors

• Specific transcription factors

- increase the level of transcription

- activators bind to enhancers (DNA


sequences
that enhance transcription)

- coactivators bridge activators with general


transcription factors
Activators and Coactivators
• Binding of activators to enhancers causes
DNA to bend

• This positions
activators bound
to the enhancers
closer to the
general transcription
factors and RNA
polymerase II

• Some activators interact with coactivators,


increasing the level of transcription
DNA Packaging
• DNA wound around histone proteins to form
nucleosomes

• Nucleosomes may block access of transcription


factors to the promoter
Histone Acetylation
• Histone acetyltransferases add acetyl groups to the
tails of histones in nucleosomes, allowing gene
transcription to take place

• Histone deacetylases remove acetyl groups from


histone tails, making promoter regions inaccessible
to transcription factors
DNA Methylation

• Involves the addition of methyl group to the


cytosine, which may block binding of
transcription factors to the promoter
Posttranscriptional Control in Eukaryotes

• Gene expression can be controlled after


transcription with

- small RNAs

• microRNAs (miRNAs) and small interfering


RNAs (siRNAs)

- alternative splicing

- mRNA degradation
miRNAs

1. microRNA gene is transcribed by RNA polymerase II into pri-microRNA • Production of miRNA


(primary microRNA)
begins in the nucleus
2. Folds back on itself, forming
a stem-loop structure

• Ends in the cytoplasm


3. Endonuclease cleaves stem-loop where endonuclease
region into pre-microRNA
(microRNA precursor) Dicer cleaves pre-
4. Pre-microRNA is exported microRNA into a ~22
from the nucleus bound to
export factor Exportin 5

nt functional miRNA
that represses gene
expression
Effect of miRNAs
• miRNA bins to the
RNA induced
silencing complex
(RISC)

• RISC, guided by
antisense single-
stranded miRNA,
recognizes target
mRNA with
complementary
sequence, leading
to mRNA cleavage
and translation
inhibition
siRNA
• RNA interference (RNAi) - type of gene silencing in
which siRNAs bind to mRNA and target its degradation

• Production similar to
miRNAs, but siRNAs arise
from long, exogenous
double-stranded RNA

• Dicer cuts yield multiple


siRNAs, which bind to
RISC

• Target mRNA is cleaved


Alternative RNA Splicing
• Single primary RNA transcript can be spliced into
different mRNAs by the inclusion of different
sets of exons

• Same gene makes calcitonin in the thyroid and


calcitonin-gene related peptide (CGRP) in the
hypothalamus
More Posttranscriptional Controls in Eukaryotes
• Selection of which mRNAs are translated

- translation factors are modified and either promote


or inhibit translation by ribosomes

- translation repressor proteins shut down


translation by binding to the beginning of the
transcript, blocking attachment to the ribosome

• Selectively degrading mRNA transcripts

- mature mRNA molecules have various half-lives


depending on the gene and the location (tissue) of
expression
Posttranslational Control of Gene Expression
• Modifications made to polypeptides

- proper folding

- glycosylation (attachment of a sugar molecule)

- phosphorylation (attachment of a phosphate group)

• Degradation of proteins:

- proteases degrade proteins by breaking peptide


bonds

- ubiquitination (addition of ubiquitin)


Ubiquitination

• Proteins marked
specifically for
destruction with
ubiquitin that is
attached by
ubiquitin ligase

• Degradation of
proteins marked
with ubiquitin
occurs at the
proteasome

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