Chapter 13

GENE
REGULATION
CONTENTS OF THIS CHAPTER
1. Overview of Gene Regulation
2. Regulation of Transcription in Bacteria
3. Regulation of Transcription in Eukaryotes: Roles of
Transcription Factors and Mediator
4. Regulation of Translation in Eukaryotes: Changes in
Chromatin Structure and DNA Methylation
5. Epigenetic Gene Regulation
6. Regulation of RNA Modification and Translation in
Eukaryotes
I. OVERVIEW OF
GENE REGULATION
1.Bacteria Regulate Genes in Response to Changes in their evironment
E.coli requires ‘transporter’ named “lactose permease” and enzyme β-galactosidase to

utilize lactose.
The amount of these proteins rely on the presence of lactose in the environment.
2.Eukaryotics Gene Regulation Produces Different Cell Types in a
Single Organism
E. Gene regulation is responsible for producing different types of cells within a
multicellular organism.
For example, three cell types(neuron, skin cell and muscle cell ) have same
genome-they carry the same set of genes.
But their proteomes—the collection of proteins they make—are quite different.
Gene regulation plays a major role in determining the proteome of each cell type.
3.Eukaryotic Gene Regulation Enables Multicellular Organism
To Proceed through Development Stages
In human, gen regulation play a role in ensuring
that an embryo and fetus get the proper amount of
oxygen.
4.Gene Regulation Occur At Different Points in Process from DNA
to protein
In bacteria, gen regulation most commonly occur at
level of transcription.
In eukaryotics, gen regulation occur in many level:
transcription, RNA modification, translation and
after translation is completed.
II. REGULATION
OF
TRANSCRIPTION
IN BACTERIA
1.Transcriptional Regulation Involves Regulatory Transcription
Factors and Small Effector Molecules
2. The lac Operon Contains Genes That Encode Proteins Involved in
Lactose Metabolism
3. The lac Operon Is Under Negative Control by a Repressor Protein
4.The lac Operon Is Also Under Positive
Control by an Activator Protein
Lac Operon is also positively regulated by an activator

catabolic activator protein(CAP), and CAP is controlled
by a small effector molecule, cyclic AMP (cAMP).
4.The lac Operon Is Also Under Positive
Control by an Activator Protein
5.The trp Operon Is Under Negative Control by a Repressor Protein
The trp Operon regulated by a repressor protein that is encoded by the trpR gene.
The ability of the trp repressor to bind to the trp operator is controlled by tryptophan.
III. REGULATION OF TRANSCRIPTION
IN EUKARYOTES:
Roles of Transcription
Factors and Mediator
COMPARE TRANSCRIPTION
between bacteria and eukaryotes
Bacteria Eukaryotes
+ activator and repressor proteins are involved in regulating genes by influencing the
ability of RNA polymerase to initiate transcription
+ eukaryotic genes are regulated by small effector molecules
+ operons +genes are almost always organized

individually
+gene regulation tends to be more intricate
Combinatorial Control
- Is the phenomenon that eukaryotic genes are regulated by many
factors
- Common factors that contribute to combinatorial control:
Activators Chromatin
structure
Effector
molecule
DNA
Repressors
methylation
1. Eukaryotic Structural genes have a core
promoter
and Regulatory Element
Enhancer
Silencer
2. RNA Polymerase II,
General Transcription Factors, and Mediator are
needed to transcribe Eukaryotic structural genes.
Regulatory
transcription
factor
3. Activators and Repressors
May Influence the Function of GTFs or
Mediator
- Regulatory transcription factors binds to enhancers or

silencers, and regulate the rate of transcription of genes
- Affecting
the function
of GTFs
- Affecting
the function
of mediator
IV. Changes in Chromatin
Structure and DNA
Methylation
1. Transcription Is Controlled by Changes
in Chromatin Structure
What is structure of chromatin ?
Chromatin is a complex of
macromolecules composed of DNA,
RNA and protein, which is found inside
the nucleus of eukaryotic cells
What is structure of chromatin ?
+ Nucleosome: a bead like structure
which is a segment of DNA that is
wrapped around the histone protein
+ Histone : A protein which is DNA
wrapped around and formed into
structural component called
Nucleosome
1. One way to change chromatin structure is through ATP-dependent
chromatin-remodeling complexes, which are a group of proteins that alter
chromatin structure.
2. How do ATP-dependent chromatin-remodeling complexes change chromatin
structure?
⮚One result is that these complexes may bind to chromatin and change the
locations of nucleosomes
⮚ A second effect is that remodeling complexes may evict histone octamers
from the DNA, there by creating gaps where nucleosomes are not found
⮚ A third possibility is that chromatin-remodeling complexes may change the

composition of nucleosomes by removing standard histone proteins from an
octamer and replacing them with histone variants
2. Histone Modifications Affect Gene
Transcription
Nucleosome components :
1. Nucleosome core +histone H1
(in higher eukaryotes +linker DNA (0-
50bp)
2. The nucleosome core contains

✔ An octamer of 2 each of the core
histones (H2A,H2B,H3 &H4)
✔ 146 bp of DNA wrapped 1.75 turm
2. Histone Modifications Affect
Gene Transcription
QTS: How do histone modifications affect
gene transcription ?
There are two opposing effects that histone

modifications may have with regard to
chromatin structure.
There are :
Histone acetylation and deacetylation
3. Eukaryotic Genes Are Flanked by
Nucleosome-Free Regions
1. The figure show a common pattern of nucleosome organization

3. Eukaryotic Genes Are Flanked by
Nucleosome-Free Regions
1. The figure show a common pattern of nucleosome organization

2. For active genes or those genes that can be activated, the core promoter
is found at a nucleosome-free region (NFR), which is a site that is
missing nucleosomes
3. The NFR is flanked by two nucleosomes that are termed the –1 and +1
nucleosomes.
4. Transcriptional Activation Involves Changes
in Nucleosome Locations, Composition, and
Histone Modifications
What is the method of this problem?
● A key role of certain activators is to recruit ATP-dependent chromatin
remodeling complexes and histone-modifying enzymes to the promoter
region of eukaryotic genes.
● Though the order of recruitment may differ among specific activators,
this appears to be critical for transcriptional initiation and elongation
A simplified model for the transcriptional activation of a eukaryotic structural gene
5. DNA Methylation Inhibits
Gene Transcription
Definition DNA Methylation : is a biological

process by which methyl groups are added
to the DNA molecule
DNA methylation usually inhibits the
transcription of eukaryotic genes, particularly
when it occurs in the vicinity of the promoter.
5. DNA Methylation Inhibits
Gene Transcription
How does DNA methylation inhibit
transcription?
There are two general ways:
⮚ Methylation of CpG islands may prevent
an activator from binding to an enhancer
element, thus inhibiting the initiation of
transcription
⮚ Methylation inhibits transcription is by

altering chromatin structure. Proteins
known as methyl-CpG-binding proteins
bind methylated sequence
V. Epigenetic Gene
Regulation
1. Definition
• was first coined by C.Waddington in

1941 .
• Involves changes in gene expression

that can be passed from cell and are
reversible, but does not involve a
change in the base sequence of DNA.
Conrad Waddington
Gene expression can be regulated by chemical modifications to chromosomes.
These are known as epigenetic changes.
chemical tag
● Epigenetic change occur during development of an organism, they
can be caused by environmental factor.
Diet Toxin Temperature

● When a cell divides to make daughter cells, many of these chemical tags are also
passed on to the next cell.
● This mean that epigenetic changes may be heritable. It calls epigenetic

inheritance.
Mitosis
● 2. Different types of molecular changes underline
epigenetic gene regulation
● 3. Factor that promote epigenetic changes
1.Genomic imprinting
● Mono-allelic gene expression

● Exclusive expression of certain gene from one parent
only
● Imprinting - methylation pattern/mark
● Pre-implantation embryos - unmethylated cytosines
2. X-chromosome inactivation
● Females have two X chromosomes, males have X

and Y X-chromosome inactivation results in one of other of two X
● Extra genes in females due to two X chromosomes chromosomes becoming inactivated (solid) in each cell while the
● Dosage compensation achieved by X inactivation other remains active (open)
● Inactivated X chromatin structure - Barr body -
heterochromatin
VI. Regulation of RNA
Modification and
Translation
in Eukaryotes
Learning Outcomes
I II III
Explain how RNA-binding proteins
Outline the process of alternative Describe how RNA interference
regulate the translation
splicing, and explain how it regulates the expression of
of specific mRNAs, using the
increases protein diversity. genes.
regulation of iron absorption in
mammals as an example.
1. Alternative Splicing of Pre-mRNAs
Increases Protein Diversity
In eukaryotes, a pre-mRNA transcript is

modified before it becomes a mature
mRNA .When a pre-mRNA has multiple introns
and exons, splicing may occur in more than one
way, resulting in the production of two or more
different polypeptides.
α-tropomyosin
Alternative splicing of the rat α-tropomyosin pre-mRNA.
2. Genomes & Proteomes Connection
Alternative Splicing Tends to Be More Prevalent
in Complex Eukaryotic Species
Compares six species:

- A bacterium (Escherichia coli),
- A eukaryotic single-celled organism (yeast—
Saccharomyces cerevisiae),
- A small nematode worm (Caenorhabditis elegans),
- A fruit fly (Drosophila melanogaster),
-A flowering plant (Arabidopsis thaliana),
- A human (Homo sapiens).
RNA Interference Blocks the
Expression of mRNA
MicroRNAs (miRNAs) and short-interfering RNAs ,(siRNAs)

are RNA molecules that are processed to a small size, typically 22
nucleotides in length, and silence the expression of preexisting
mRNAs.
A pre-miRNA is first synthesized as a single-stranded

molecule that folds back on itself to form a hairpin
structure .
The 22-bp sequence becomes part of a complex called the

RNA-induced silencing complex (RISC), which also
includes several proteins .
Mechanism of action of microRNA (miRNA )

4. RNA Interference Blocks the Expression of
mRNA
Upon binding, two different things may happen.
1 2
When the miRNA When an siRNA and mRNA
and mRNA are not a perfect match or are a perfect match or highly complementary,
are only partially complementary, the mRNA is cut into
translation is inhibited . pieces and then degraded.
Both miRNA and siRNA have the same effect—the expression of the mRNA is silenced.
RNA interference (RNAi), because the miRNA interferes with the proper expression of an
mRNA .
5. The Prevention of Iron Toxicity in Mammals
Involves the Regulation of Translation
Iron regulatory protein (IRP ) Iron regulatory element (IRE)
The mRNA that encodes ferritin is controlled When the iron level in the cytosol is
by an RNA binding protein known as the iron low and more ferritin is not needed,
regulatory protein (IRP) . IRP binds to a regulatory element
within the ferritin mRNA known as
the iron regulatory element (IRE).
Translational regulation of
ferritin mRNA by the
iron regulatory protein (IRP)
● Due to base pairing, it forms a stem-loop

structure .The binding of IRP to the IRE
inhibits translation of the ferritin mRNA .
Translational regulation of
ferritin mRNA by the
iron regulatory protein (IRP)
● When iron is abundant in the cytosol, the iron
binds directly to IRP, which changes its
conformation and prevents it from binding to
the IRE . Under these conditions, the ferritin
mRNA is translated to make more ferritin
protein.
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GENE

E.coli requires ‘transporter’ named “lactose permease” and enzyme β-galactosidase to

Lac Operon is also positively regulated by an activator

+ operons +genes are almost always organized

- Common factors that contribute to combinatorial control:

- Regulatory transcription factors binds to enhancers or

⮚ A third possibility is that chromatin-remodeling complexes may change the

2. The nucleosome core contains

There are two opposing effects that histone

1. The figure show a common pattern of nucleosome organization

1. The figure show a common pattern of nucleosome organization

Definition DNA Methylation : is a biological

⮚ Methylation inhibits transcription is by

• was first coined by C.Waddington in

• Involves changes in gene expression

Diet Toxin Temperature

● This mean that epigenetic changes may be heritable. It calls epigenetic

● Mono-allelic gene expression

● Females have two X chromosomes, males have X

In eukaryotes, a pre-mRNA transcript is

Compares six species:

MicroRNAs (miRNAs) and short-interfering RNAs ,(siRNAs)

A pre-miRNA is first synthesized as a single-stranded

The 22-bp sequence becomes part of a complex called the

Mechanism of action of microRNA (miRNA )

Iron regulatory protein (IRP ) Iron regulatory element (IRE)

● Due to base pairing, it forms a stem-loop

CREDITS: This presentation template was created by Slidesgo, including

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