This document discusses the regulation of gene expression in prokaryotes and eukaryotes. In prokaryotes, genes are often clustered together in operons and regulated by a single promoter. The lac operon is described as an example, involving negative regulation by the lac repressor in the absence of lactose and positive regulation in the presence of lactose. In eukaryotes, gene expression is regulated at the DNA, transcriptional, post-transcriptional, translational, and post-translational levels. Mechanisms of regulation include chromatin remodeling, promoter/enhancer binding, RNA processing, mRNA transport, and translational control involving elements like iron response elements. Precise regulation allows the production of diverse proteins

1. Regulation of gene
expression
Prof (Dr.) V. P.
Acharya
MBBS, MD, PhD

2. Gene expressed in the form of
protein →Gene expression

3. Negative Regulation
X
Positive Regulation
X

4. Types of genes
• Inducible gene– expressed
when a specific positive
regulatory substance-
inducer/activator present
• Constitutive gene– Expression
not regulated– expressed at a
constant rate
Housekeeping genes

5. Regulation of gene expression in
Prokaryotes
• Simple, genes clustered together
• Single promoter required
• Genes involved in a metabolic
process are often present in a
linear fashion
↓
Operon
Ex- lac operon, Ara operon, Gal
operon

6. Lac Operon

8. • Regulatory gene–Lac i– produces
repressor protein
• Promoter site P– For binding of RNAP
• Operator site O– lac repressor binds to
this site and blocks initiation of
transcription
• Structural genes Z, Y & A– Code for β-
galactosidase, galactoside permease
& thiogalactoside transacetylase

9. • Normally E. coli depends on
glucose
• Absence of glucose– utilises
lactose
• β- galactosidase– essential in
the metabolism of lactose
• Permease– transport of lactose
across the membrane
• Transacylase– detoxification of
substances that are carried by
the permease

10. Mechanism of regulation
1. Negative regulation by lac
repressor in absence of lactose
and presence of glucose
2. Positive regulation in presence
of lactose and absence of
glucose
3. Positive control by catabolite
repression, in presence of both
lactose and glucose

13. Glucose inhibits adenylyl cyclase
↓
↓cAMP formed
↓
CRP-cAMP complex less formed
↓
↓Transcription

14. Bacterium starved of a source of
carbon
↓
cAMP accumulates
↓
Binds to CRP
↓
PIC formed at the promoter site

15. Regulation of gene expression in eukaryotes

16. • DNA level
• Transcriptional level
• Post-transcriptional level
• Translational level
• Post-translational level

17. DNA level gene regulation
• DNA with histones- Nucleosomes
• Nucleosomes- resistant to nuclease attack
• Only 2% DNA will be expressed
• After post-transcriptional and post-
translational modification very specific
proteins are formed- strict regulation
• Acetylation of Histones- expresses
Deacetylation- represses

18. DNA-protein interactions
• Regulatory proteins
bind to DNA control
sites – mediated by
certain motifs
involving H and Van
der Waal’s bonds
• Helix-turn-helix motif
• Zinc finger motif
• Leucine zipper motif

19. Helix-turn-helix motif
• 20 AA
• 2 α- helices separated by a β-
sheet
• Lac repressor, Trp-
repressor and CAP act
via this
Helix-turn-helix motif

20. Zinc finger motif
• Centrally placed Zn
• 30 AA
• 4 AA form co-ordination with
Zn
• Receptors of Group I hormones
(Steroid & Thyroid)
• Mutation of a single AA in a
zinc finger of calcitriol receptor
protein- Rickets Zinc finger motif

21. Leucine zipper motif
• Large no of basic AA are there
• Associate with negatively
charged phosphates in DNA
• Leucine at 7th position of α-
helices
• Enhancer binding proteins
FOS & JUN- contain this motif

22. Gene regulation at DNA level
• Gene amplification
• Gene rearrangement
• Gene loss
• Methylation of DNA

23. Gene amplification
In order to produce large no. of
specific proteins the genes are
amplified
During some stage of
development
Ex– Fruit fly egg shell
Methotrexate drug resistance- amplify genes
coding for DHFR enzyme

24. Gene rearrangement
• Segments of DNA can
move from one place to
another on the same
DNA
• Transposition
• Ex– B-cells producing
antibodies

25. Gene loss
• If genes completely or partially
deleted, no functional proteins
can be generated
• Ex—Mature RBC devoid of
nucleus

26. Methylation of DNA
• Maintains inactive
heterochromatin (Non-
transcriptional chromosome)
• Permanently turned off genes
• Removal of methyl groups
activates the genes
• Ex—Barr body

27. Transcriptional regulation
• Chromosomal packaging
• Individual gene regulation

28. Chromosomal packaging
• Tightly packaged–
heterochromatin– inaccessible
to transcription
• Lightly packaged– Euchromatin-
-- accessible to transcription

29. Individual gene regulation
• Similar to operons in
prokaryotes
• Regulatory factors
• Promoter regions, enhancers,
silencers
• DNA binding domains– zinc-
finger motifs, helix-turn-helix,
leucine zipper motifs

30. RNA processing
• Post-transcriptional
modifications
Alternate mRNA processing
3.2 million DNA base pairs
1.5% encode proteins < = > 98.5% not protein encoding
~ 30,000 genes encoding 100,000 - 200,000 proteins
How are 100,000 to 200,000 proteins produced from 30,000 genes???
•Alternate splicing may lead to production of different proteins
•Single gene expression can lead to diverse molecule production

31. Alternative pre-mRNA Splicing
Ex- Thalassaemia

32. Regulation at mRNA transport level
• Information pathway-
checkpoint
Degradation of mRNA
•Biological half-life of mRNA is pre-
decided
•If an encoded protein is not needed then
mRNA degradation is favoured

33. Gene regulation at
Translational level
• Proteins involved in iron metabolism-
Transferrin, ferritin, hemosiderin, storage
and transport proteins- regulation at
translation level
• Iron response elements- present in mRNAs
• Iron binding proteins bind to IRE- repress
or stimulate the genes

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