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REGULATION OF GENE EXPRESSION

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REGULATION OF GENE EXPRESSION CREB the most important protein that you have never heard of Implicated in Cell proliferation Cell differentiation Spermatogenesis ... – PowerPoint PPT presentation

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Title: REGULATION OF GENE EXPRESSION


1
REGULATION OF GENE EXPRESSION
2
WHY REGULATE GENE EXPRESSION??
  • Adaptation
  • (Energy Conservation)
  • Development and differentiation

3
GENE EXPRESSION IN DIFFERENT CELLS
Pancreatic cells
Blood cells
Muscle cell
Genes for
Glycolysis ON ON ON ON ON
Insulin OFF OFF ON OFF OFF
Glucagon OFF ON OFF OFF OFF
Hemoglobin OFF OFF OFF OFF ON
alpha cells beta cells
WBCs RBCs
4
A PROKARYOTIC AND EUKARYOTIC CELL
5
REGULATION OF GENE EXPRESSION - PROKARYOTES
6
THE OPERON
Operon
DNA
Protein 1
Protein 2
Protein 3
7
REPRESSORS
Regulatory gene
mRNA
Repressor
RNA polymerase
Operator
Gene 2
Gene 3
Gene 1
Promoter
5
3
No transcription
No protein products
8
REGULATORY MECHANISMS
  • INDUCTION
  • Repressor is INACTIVATED through inducers to
    INITIATE / INDUCE transcription
  • REPRESSION
  • Repressor is ACTIVATED through corepressors to
    PREVENT / REPRESS transcription

9
INDUCTION
Active repressor
No transcription, translation
Inducer
Inactive repressor
10
REPRESSION
No transcription, translation
11
  • GENE REGULATION IN EUKARYOTES

12
Gene Regulation Can Take Place at Many Levels
  • Chromosome
  • Transcription
  • Processing of transcripts
  • Translation

13
  • GENE REGULATION AT THE CHROMOSOMAL LEVEL

14
Two Types of Chromatin
  • HETEROCHROMATIN Trancriptionally inactive
  • tightly condensed
  • EUCHROMATIN
  • Transcriptionally active
  • Relatively relaxed

15
CHROMATIN STRUCTURE
16
EFFECT OF CHROMATIN STRUCTURE ON TRANSCRIPTION
GENE IS ACTIVE
GENE IS INACTIVE
17
Histone Acetylation
18
Histone Acetylation
19
DNA Methylation
20
(No Transcript)
21
X-Inactivation
  • Inactive X-Chromosome (Barr body)
  • Underacetylated at H4
  • Hypermethylated

22
X-inactivation in humans
  • Red-green color blindness
  • Males fully color blind
  • Females mosaic retinas
  • Anhidrotic ectodermal dysplasia
  • Males absence of teeth, lack of sweat glands
  • Females random patterns of tissue with or
    without sweat glands

23
Arrangement of DNA
24
(No Transcript)
25
Antibody Diversity
  • Light chains
  • Up to 300 Variable, 4 Joining and 1 Constant
    region
  • 300 x 4 1, 200 light chains
  • Heavy chains
  • Up to 500 Variable, 4 Joining and 12 Diversity
    regions and 12 constant regions
  • 500 x 4 x 12 24, 000 light chains

1200 x 24,000 28,800,000 antibody molecules
26
Mobile Genetic Elements - Transposons
27
  • REGULATION AT THE LEVEL OF TRANSCRIPTION

28
  • GTFs only produce a basal level of transcription
    i.e. very low
  • Gene-specific factors (activators) are further
    required to regulate the activity of gene
    expression

29
Enhancers/Silencers
  • Upstream or downstream
  • Close to the promoter or thousands of base pairs
    away
  • On either of the two strands of DNA
  • Act through intermediary or gene specific
    transcription factors proteins
  • Enhancers activate transcription
  • Silencers deactivate transcription

30
Enhancers/Silencers
31
Response Elements
  • Enhancers contain response elements that are
    responsive to certain metabolic factors
  • Cyclic AMP response element (CRE)
  • Glucocorticoid response element (GRE)
  • Heat shock element (HSE)
  • REs bind transcription factors produced under
    certain cell conditions to activate several
    related genes

32
cAMP Response Element (CRE)
  • 5- TGACGTCA -3
  • 3- ACTGCAGT -5

33
cAMP Response Element (CRE)
  • cAMP second messenger of several hormones
    (glucagon, epinephrine)
  • cAMP ? protein kinase A ?
  • protein kinase A phosphorylates the cAMP RESPONSE
    ELEMENT BINDING PROTEIN (CREB)
  • Phosphorylated CREB binds to the CRE binding
    protein (CBP)
  • CBP connects CREB to the basal transcription
    machinery and promotes gene activation

34
CREB the most important protein that you have
never heard of
  • Implicated in
  • Cell proliferation
  • Cell differentiation
  • Spermatogenesis
  • Release of somatostatin (inhibitor growth
    hormone)
  • Development of T lymphocytes
  • Metabolism of the pineal gland
  • Adaptation to physical stress
  • Transcription of metabolic enzymes
  • Critical in learning and long term memory

35
Activation of CREB
36
Glucocorticoid Response Element
37
GENE REGULATION BY PROCESSING OF TRANSCRIPTS
38
Alternative Splicing
39
RNA EDITING
40
Regulation of Translation by Phosphorylation
41
mRNA Stability
42
Regulation of Transferrin Expression
43
Regulation of ferritin expression
44
RNA Interference
  • will be done with therapeutics

45
  • The End!
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