BIOT406

Bioinformatics

Lecture : GeneRegulation and Expression

By
Adeena Tahir
 Learning Objectives

• Genes and Regulatory Elements

• Levels of Gene Regulation
• Gene Regulation in Eukaryotic Cells
• Chromatin Remodeling
• Histone Modifications
• RNA splicing
• The degradation of RNA
• Activators and Repressors in gene regulation
• Role of Epigenetic Effects
 What is a gene ?

• Gene is the basic physical and functional unit of

heredity.
• Each gene is located on a particular region of a
chromosome and has a specific ordered sequence
of nucleotides.
• Each cell in the human body contains about 25,000
to 35,000 genes.
• Genes carry the genetic information that determines
your traits, which are features or characteristics that
are passed on from parents to offspring.
 Genes and Regulatory Elements

The Regulation of Gene Expression is critical for all

organisms:

• Structural genes: encoding proteins

• Regulatory genes: encoding products that interact

with other sequences and affect the transcription and
translation of these sequences

• Regulatory elements: DNA sequences that are not

transcribed but play a role in regulating other
nucleotide sequences
 Genes and Regulatory Elements

• Constitutive expression: continuously expressed

under normal cellular conditions

• Positive control: stimulate gene expression

• Negative control: inhibit gene expression

 Gene Expression

● “The phenotypic manifestation of genes by

the processes of transcription and
translation”.

● Regulation of gene occurs at many points

during the transcription and translation
processes and involves epigenomic
compounds.

● Complex and highly regulated.

 Proteins involved in gene expression

Messenger proteins Structural proteins

Transmit signals to coordinate Provide structure and support for
biological processes that occur cells. Actin filaments and
between different cells, tissues microtubules are examples of
and organs. Hormones (e.g, structural proteins. There are
insulin, oxytocin) are great three types of structural proteins:
examples of messenger proteins. fibrous, globular and membrane.
Fibrous proteins form hair, nails
and skin.
 Continue….

Enzymes Transport proteins

Catalyze chemical reactions in Bind and carry atoms and small
cells (e.g, muscle contraction). molecules. Hemoglobin is a
Enzymes assist with bodily transport protein in red blood
functions such as digestion and cells that is used to carry oxygen
DNA replication from the lungs to other tissues.
▪ Gene regulation is the turning on and
off of genes.

▪ Gene expression is the overall

process of information flow from
genes to proteins.

▪ The control of gene expression

allows cells to produce specific
kinds of proteins when and where
they are needed.
 Levels of Gene Regulation

Points where genes can be regulated

-Through the alteration of DNA
or chromatin structure
- At the level of transcription
- mRNAprocessing
- Regulation of RNAstability
- Translation control
- Posttranslational modification
Gene regulation is important not only during
development but also in mediating common
variation between individuals, diseases, birth
defects, and evolution.
 Gene Regulation and Nutrition:
Development (organs, cell
types)`

Muscle Liver (Diseased)

Fat

Embryo
Brain
Intestines

With respect to nutrition, gene regulation is important to guide

the development of organs, tissues, and cell types required to
ingest, digest, and metabolize nutrients.
Genes can be regulated at many levels

DNA RNA PROTEIN

TRANSCRIPTION TRANSLATION

The “Central Dogma”

 Complex assemblies of proteins control
eukaryotic transcription
▪ Prokaryotes and eukaryotes employ regulatory proteins
(activators and repressors) that
• Bind to specific segments of DNA and

• Either promote or block the binding of RNA polymerase, turning the

transcription of genes on and off.

▪ In eukaryotes, activator proteins seem to be more important than

repressors. Thus, the default state for most genes seems to be
off.

▪ A typical plant or animal cell needs to turn on and

transcribe only a small percentage of its genes.
 Complex assemblies of proteins control
eukaryotic transcription

▪ Eukaryotic RNA polymerase requires the assistance of proteins

called transcription factors. Transcription factors include

• Activator proteins, which bind to DNA sequences called enhancers

and initiate gene transcription. The binding of the activators leads to
bending of the DNA.

• Other transcription factor proteins interact with the bound activators,

which then collectively bind as a complex at the gene’s promoter.

▪ RNA polymerase then attaches to the promoter and

transcription begins.
 Enhancers Promoter
Gene

DNA
Activator
proteins
Transcription
factors
Other
proteins

RNA polymerase

Bending
of DNA

Transcription
 Complex assemblies of proteins control
eukaryotic transcription

▪ Repressor proteins
• May bind to DNA sequences (silencers) and

• Inhibit transcription.

▪ Coordinated gene expression in eukaryotes often depends on

the association of a specific combination of control elements
with every gene of a particular metabolic pathway.
 Eukaryotic RNA may be spliced in more than
one way

▪ Alternative RNA splicing

• Produces different mRNAs from the

same transcript,

• Results in the production of more than

one polypeptide from the same gene

• May be common in humans

 Exons

DNA 1 2 3 4 5

Introns Introns

Cap Tail
RNA
transcript 1 2 3 4 5

RNAsplicing

or
mRNA 1 2 3 5 1 2 4 5
Later stages of gene expression are also subject
to regulation

▪ After mRNA is fully processed and transported to the

cytoplasm, gene expression can still be regulated by
• Breakdown of mRNA,

• Initiation of translation,

• Protein activation, and

• Protein breakdown
 Multiple mechanisms regulate gene expression
in eukaryotes

▪ Multiple control points exist where gene expression in

eukaryotes can be
• Turned on or off or

• Speeded up or slowed down.

▪ These control points are like a series of pipes carrying

water from your local water supply to a faucet in your
home. Valves in this series of pipes are like the control
points in gene expression.
 Chromosome Chromosome

DNA unpacking
Other changes to the DNA

Gene DNA

Gene
Transcription
Exon
RNA transcript
Intron
Addition of a cap and tail

Splicing Tail

Cap
mRNA in nucleus
Flow through
NUCLEUS nuclear envelope

CYTOPLASM
mRNA in cytoplasm CYTOPLASM

Breakdown of mRNA

Broken-
Translation down
mRNA
Polypeptide
Polypeptide

Cleavage, modification,
activation

Active protein Active

protein

Breakdown
of protein

Amino
acids
 Multiple mechanisms regulate gene expression
in eukaryotes
▪ These controls points include:
1. Chromosome changes and DNA unpacking,
2. Control of transcription,
3. Control of RNA processing including the
– Addition of a cap and tail
– Splicing
4. Flow through the nuclear envelope,
5. Breakdown of mRNA
6. Control of translation
7. Control after translation including
– Cleavage/modification/activation of proteins and
– Breakdown of protein.
Signal transduction pathways convert messages
received at the cell surface to responses
within the cell

▪ A signal transduction pathway is a series of molecular

changes that convert a signal on the target cell’s surface to a
specific response within the cell.

▪ Signal transduction pathways are crucial to many

cellular functions.
Signaling cell EXTRACELLULAR FLUID
Signaling
1 molecule

2 Receptor Plasma
protein membrane

Target cell 3

Relay Signal
proteins transduction
pathway

4
Transcription factor
(activated)

NUCLEUS

DNA

5
Transcription
mRNA

New
6 protein

CYTOPLASM Translation
 Gene Regulation in Eukaryotic Cells Takes Place at
Multiple Levels

• Chromatin remodeling
• Chromatin-remodeling complexes: bind directly to
DNA sites and reposition nucleosomes

• Histone modification
• Addition of methyl groups to the histone protein
tails
• Addition of acetyl groups to histone proteins
 Gene Regulation in Eukaryotic Cells Takes Place at
Multiple Levels

• Acetylation of histones controls flowering in

Arabidopsis

• Flowering locus C (FLC) gene

• Flowering locus D (FLD) gene

 Gene Regulation in Eukaryotic Cells Takes Place at
Multiple Levels

• Transcriptional activators and repressors

• Bind to silencers
• Enhancers and Insulators
• Enhancer: DNA sequence stimulating transcription
from a distance away from promoter
• Insulator: DNA sequence that blocks or insulates the
effect of enhancers
Gene Regulation in Eukaryotic Cells
Takes Place at Multiple
Levels
 Gene Regulation in Eukaryotic Cells Takes Place at
Multiple Levels

Gene regulation through RNA splicing

• Alternative splicing in the T-antigen gene

• Alternative splicing in Drosophilia sexual

development
 Epigenetic Effects
Influence Gene
Expression

• Epigenetic Effects
• Changes induced by maternal
behavior
• Effects caused by prenatal exposure
• Effects in monozygotic twins

• Molecular Mechanisms of
Epigenetic Changes
• DNA methylation is maintained
from generation to
• generation
 Summary

• Genes and Regulatory Elements

• Levels of Gene Regulation
• Gene Regulation in Eukaryotic Cells
• Chromatin Remodeling
• Histone Modifications
• RNA splicing
• The degradation of RNA
• Activators and Repressors in gene regulation
• Role of Epigenetic Effects
 Take Home Message

Narrated Anas bin Malik The Messenger of Allah

(S.A.W.W) said that:

“Allah has HIS own people among mankind”.

The Sahaba said: “O Messenger of Allah (S.A.W.W)

Who are they?”

He (S.A.W.W) said: “The people of the Quran, the

people of Allah and those who are closest to Him.”

Sunnan Ibn e Maja: Hadith 215

 Thankyou...!

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