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REGULATION OF GENE EXPRESSION. WHY REGULATE GENE EXPRESSION?? Adaptation (Energy Conservation) Development and differentiation.

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Presentation on theme: "REGULATION OF GENE EXPRESSION. WHY REGULATE GENE EXPRESSION?? Adaptation (Energy Conservation) Development and differentiation."— Presentation transcript:

1 REGULATION OF GENE EXPRESSION

2 WHY REGULATE GENE EXPRESSION?? Adaptation (Energy Conservation) Development and differentiation

3 GENE EXPRESSION IN DIFFERENT CELLS Muscle cell Pancreatic cells alpha cells beta cells Blood cells WBCs RBCs Genes for GlycolysisON InsulinOFF ONOFF GlucagonOFFONOFF HemoglobinOFF ON

4 A PROKARYOTIC AND EUKARYOTIC CELL

5 REGULATION OF GENE EXPRESSION - PROKARYOTES

6 THE OPERON DNA Promoter Gene 1 Gene 2Gene 3 Structural Genes 53 AUG UAAUGA UAG Polycistronic mRNA Protein 1Protein 2Protein 3 Operon

7 REPRESSORS 3 mRNA Promoter Gene 1 Gene 2Gene 3 5 Operator No transcription No protein products Regulatory gene Repressor RNA polymerase

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 Inducer Inactive repressor Active repressor No transcription, translation Transcription Translation

10 REPRESSION Inactive repressor Corepressors Transcription Translation No transcription, translation Active repressor

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 Control region outside nucleosome GENE IS ACTIVE Control region within nucleosome GENE IS INACTIVE

17 Histone Acetylation HAT

18 Histone Acetylation

19 DNA Methylation

20

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

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 – second messenger of several hormones (glucagon, epinephrine) cAMP = protein kinase A cAMP RESPONSE ELEMENT BINDING PROTEINprotein 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 cAMP Response Element (CRE)

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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