GENETICS Chapter 10 - From Gene To Protein - Regulation of Gene Expression - EDITING

REGULATION OF
GENE EXPRESSION
General principles of gene regulation
• Genes can be regulated at any level, including transcription, RNA
processing, translation, and post-translation.
• Control of transcription is an important mechanism of gene regulation.
• Transcriptional control can be negative (''on unless turned off") or positive
("off unless turned on"); many genes include regulatory regions for both
types of regulation.
• Most genes have multiple, overlapping regulatory mechanisms that
operate at more than one level, from transcription through post-
translation.
• In prokaryotes, the genes coding for the enzymes in a metabolic pathway
are often clustered in the genome and controlled jointly by a regulatory
protein that binds with an "operator" region at the 5' end of the cluster.
This type of gene organization is known as an operon.
• In eukaryotes, genes are not organized into operons. Genes at dispersed
locations in the genome are coordinately controlled by one or more
"enhancer" DNA sequences located near each gene that interact with
transcriptional activator proteins that enable transcription of each nearby
gene to occur.
• Level of gene control
▫ Alteration of gene structure
(DNA methylation,
chromatine change …)
▫ Level of transcription for the
cellular economy
▫ mRNA procesing (modified
mRNA can be translated)
▫ RNA stability
▫ Level of translation
▫ Protein processing
• Gene and regulatory elements
▫ Structural genes: produce proteins for the metabolism
▫ Regulatory genes: produce RNA or proteins that interact
with other sequence (regulatory sequence) that affect the
transcription and translation
• DNA-binding proteins
▫ Bind to DNA and influence the expression of DNA
1. Gene regulation in bacterial cell
• Operon structure
▫ Genes that have related function are grouped and
are under control of 1 promoter
▫ Gene are often transcribed into one mRNA
▫ Regulatory gene produces regulatory protein that
binds to regulatory element and control the
expression of the structural gene a,b,c
• Negative and positive control: inducible and
repressible operon
▫ negative control: a regulatory protein acts as a
repressor, binding to DNA and inhibiting
transcription;
▫ positive control, a regulatory protein acts as an
activator, stimulating transcription.
• Lac mutations – home work
• Positive control and catabolite repression
▫ Bacteria prefer to metabolize glucose  when
glucose is present, genes participate in the
metabolism of other sugar are repressed –
catabolite repression
▫ Lac operon is activated only when lactose presents
and glucose is absent
Catabolite activator protein
positively controls more than
20 operons in E.coli
Glucose inhibits the enzyme adenylate

cyclase  can not synthesize cAMP
Repressible regulation in Trp operon
• Trp operon is also controlled by attenuation
▫ Repression is never complete; some transcription
is initiated even when the trp repressor is active;
repression reduces transcription only as much as
70-fold.
▫ Attenuation can further reduce transcription
another 8- to 10-fold; so together the two
processes are capable of reducing transcription of
the trp operon more than 600-fold.
• Antisense RNA in gene regulation
▫ Beside protein regulators, many RNA regulators
have been discovered
▫ Small RNA molecules bind by complement to the
particular sequence on mRNA and control the
gene expression  antisense RNA
▫ Example: antisense RNA control the expression of
ompF (produce the outer membrane protein that
functions as membrane pore that allow bacterium
to adapt the environment osmolarity)
2. Eukaryotic gene regulation
• Some common features seen in both prokaryote and
eukaryote: controlled by DNA binding proteins, contains
regulatory elements…
• Different features:
▫ Gene is not structured in operon, instead, each gene has its own
promoter
▫ Chromatin structure affects gene expression
▫ Activators are more common in eukaryotic system than in
prokaryote
▫ Regulation of gene expression in eukaryotic cells is
characterized by a greater diversity of mechanisms that act at
different points in the transfer of information from DNA to
protein.
Chromatin structure and gene regulation
• For a gene to be transcribed, DNA segment should be released
from histone complex.
▫ This relaxation allow DNAseI hydrolyse gene  DNAseI
hypersensitivity region (this is also region for biding with
regulatory factor)
• Histone acetylation
▫ Acetyl groups are added to the histone proteins by acetyl
transferase  destablize nucleosome structure  allows DNA
separate from histone
▫ Enzyme deacetylase strip acetyl group from histone  bring back
the structure of nucleosome
Biology, Campbell and Reece, 2007
• DNA methylation
▫ Heavily methylated DNA is associated with the
repression of transcription in vertebrates and plants,
whereas transcriptionally active DNA is usually
unmethylated in these organisms.
▫ DNA methylation is most common on cytosine bases
adjacent to guanine nucleotides on the same strand
(CpG);
▫ Association between DNA methylation and the
deacetylation of histones, both of which repress
transcription
Transcriptional Control in Eukaryotic Cells
• Transcriptional activators,
coactivators and repressors
• Enhancers and insulators
• Coordinated gene regulation
▫ several eukaryotic genes
may be activated by the
same stimulus
Gene Control Through Messenger
RNA Processing
• Alternative splicing
allows a pre-mRNA
to be spliced in
• multiple ways,
generating different
proteins in different
tissues
• or at different times
in development
Gene Control Through RNA Stability
• there is great variability in the stability of
eukaryotic mRNA: some persist for only a few
minutes; others last for hours, days, or even
months  result in large differences in the
amount of protein that is synthesized.
RNA Silencing
• expression of some genes
may be suppressed
through RNA silencing,
also known as RNA
interference and
posttranscriptional gene
silencing
Translational and Posttranslational Control
• The initiation of translation in some mRNAs is regulated
by proteins that bind to the mRNA’s 5 UTR and inhibit
the binding of ribosomes, similar to the way in which
repressor proteins bind to operators and prevent the
transcription of structural genes.
• Many eukaryotic proteins are extensively modified after
translation by the selective cleavage and trimming of
amino acids from the ends, by acetylation, or by the
addition of phosphates, carboxyl groups, methyl groups,
and carbohydrates to the protein)  affect the transport,
function, and activity of the proteins and have the
capacity to affect gene expression.

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REGULATION OF

Glucose inhibits the enzyme adenylate

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