This presentation deals with how gene expression is regulated in eukaryotes.

1. Regulation of Gene
Expression in
Eukaryotes
BY:
SUCHITTA. U

2. 1. Overview of gene expression
2. Differences between prokaryotic and eukaryotic gene expression
3. Regulation of gene expression at transcriptional level
3.1 Promoter regions in eukaryotes
3.2 Role of transcription factors and formation of transcription bubble
4. Enhancers
5. Regulation of gene expression by intercellular and intracellular
signals
6. Regulation of RNA processing
6.1 Splicing and Alternative splicing
7. Britten Davidson's model
CONTENTS

3. OVERVIEW OF GENE EXPRESSION
 Producing protein from information in a DNA gene is a two step
process
Transcription
Translation
TRANSCRIPTION
TRANSLATION

4. Outline of Gene Regulation
 Different cell types are from differential gene expression of an
identical genome
 Complex regulatory mechanisms for expression of specific gene
 Gene expression is regulated at each step in the modification
pathway from DNA RNA Protein
 The expression of gene is likely to be regulated at several of these
levels
The potential control levels are

5. Potential Control Levels for Regulation of Gene Expression

6. Differences between prokaryotic and eukaryotic regulation of gene
expression
Regulation of gene expression in eukaryotes differ in three important
ways from that of prokaryotes
1. Action of gene regulatory proteins
2. General transcription factors
3. Packaging of the eukaryotic DNA into chromatin
The control of gene expression occur at multiple stages but it is clear
that in eukaryotes the majority of the regulatory genes occurs in the
initiation of transcription

7. Regulation of gene expression at transcriptional level
 Promoter region of eukaryotes
Nucleotide sequence (recognition sites) for the binding of RNA polymerase
Located adjacent to the genes they regulate
Binding of numerous protein factors to initiate transcription
Transcription complex on promoter TATA Box sequence
Genes which lack TATA box has Inr (Initiator sequence) which directs RNA
polymerase to the promoter
TATA BOX TATA binding
protein (TBP)
TBP associated
factors (TAF’s)
BINDS TO BINDS TO
TFIID

8. Levels of Gene Regulation
 ROLE OF TRANSCRIPTION FACTORS AND FORMATION OF TRANSCRIPTION BUBBLE COMPLEX

9. Levels of Gene Regulation
 ROLE OF TRANSCRIPTION FACTORS AND FORMATION OF TRANSCRIPTION BUBBLE COMPLEX

10. Levels of Gene Regulation
 ROLE OF TRANSCRIPTION FACTORS AND FORMATION OF TRANSCRIPTION BUBBLE COMPLEX

11. Regulation of Gene Expresssion
 ENHANCERS CONTROL CHROMATIN STRUCTURE AND THE RATE OF
TRANSCRIPTION
Cis regulators: Regions of non coding DNA which regulate the transcription of
nearby genes
Enhancers: Increase the efficiency of transcription
Interact with the transcription factors and regulatory proteins
Responsible for full level transcription unlike promoters
Full time and tissue specific expression of genes
Alter configuration of the chromatin
Bending and looping of DNA
The transcription factors bring distant enhancers and their promoters into direct
contact
Complexes with transcription factors and polymerases
DNA looping and binding of transcription factors to the enhancers

12. Levels of Gene Regulation
INTRACELLULAR AND INTERCELLULAR SIGNALS
 Steroid hormones- Cortisol act by turning on the transcription specific set of
genes
 Through diffusion the hormone enters the target cell
 It encounters the receptor molecules which is complexed with another protein
Hsp82
 Cortisol binds to receptor release of the receptor from Hsp82
 Hormone receptor complex migrates to nucleus
 Binds to the DNA target sequences (hormone receptor elements)
 Activate the transcription
Nuclear envelope
Nucleus
Transcriptional
Activation
Transcription
Hormone
receptor
complex
Cell membrane
Receptor
Cytoplasm
Cortisol
Hsp82
DNA
binding
site
Hormonal regulation of gene expression

13. REGULATION OF RNA PROCESSING
 SPLICING
o m RNA is produced by splicing the primary transcript (pre-m RNA)
o Introns are spliced out and exons are joined together
o Eukaryotes have evolved a splicing machinery (SPLICESOME) –
several protein RNA complexes called Sn RNP’s

14. REGULATION OF RNA PROCESSING
 ALTERNATIVE SPLICING
Alternative selection of promoters
Alternative selection of cleavage/ polyadenylation sites
Intron retaining model
Exon cassette model
1
2
3
4

15. REGULATION OF RNA PROCESSING
P1 P2
Alternative selection of promoters
Alternative selection of cleavage/ polyadenylation sites
Poly A
Poly A
• Cell type specific transcription factor
• Genes for myosin light chain, amylase are regulated in this manner
• Immunoglobulin gene transcript
• Tropomyosin (cytoskeleton proteins) calcitonin/CGRP genes

16. ALTERNATIVE SPLICING
 If intron retained in coding regions- encode amino acids in frame with the
nearby exon or stop codon in the reading frame will cause the protein to be
non functional.
 Rarest mode in mammals
 Some exons can be excluded or included
 Neural cell adhesion molecules (N-CAMs), troponin-T (Muscle cells)
Intron retaining model
Exon cassette model

17. BRITTEN-DAVIDSON’S MODEL FOR REGULATION OF GENE EXPRESSION
 Hypothesis proposed by R.J. Britten and E. H. Davidson for the regulation of
protein synthesis
 Gene battery model
 Four classes of sequences
Producer genes: comparable to structural genes of prokaryotes (operon)
Receptor site : operator sites in operon
Integrator gene : comparable to regulator gene, synthesis of an activator RNA
Sensor site : only activated sensor sites can led to the regulation of the integrator
genes. Hormones recognize these sensor sites
Integrator and producer genes
 RNA synthesis
 Repeated numerous times
 Control the activity of large number of genes
One sensor site control a set of structural genes : Battery , One sensor site + several
integrators = transcription of several producer genes (receptor sites)
The interrelationship of thee four classes of sequences in Britten-Davidson’s
model
Signal