Control of gene expression

1. Control of gene expression • Transcriptional • Post-transcriptional • Epigenetics and long range control

2. Control of gene expression • Transcriptional • Tissue specific transcription factors • Binding of hormones, growth factors etc. to response elements • Use of alternative promoters in a single gene

3. Control of gene expression • Post-transcriptional • Alternative splicing • Alternative polyadenylation • Tissue specific RNA editing • Translational control mechanisms

4. Control of gene expression • Epigenetics and chromatin structure • Allelic exclusion (rearrangements, imprinting, X inactivation) • Long range control by chromatin structure (position effects Pax6 in aniridia) • Cell position-dependent, short range signaling

5. Control of gene expression • rRNA synthesis • Arrows indicate cleavage sites

7. Control of gene expression • Initiation of transcription (RNA pol I)

9. Control of gene expression • tRNA and 5s RNA promoter elements • Initiation of transcription (RNA pol III)

11. Control of gene expression • Conserved locations of promoter elements in eukaryotes

13. Control of gene expression • Insulin gene promoter organization • NRE negative regulatory element • CRE cAMP response element

15. Control of gene expression • HS-40 alpha-globin regulatory site • Tissue specific regulation (many sites)

17. Control of gene expression • Structural domains in transcription factors • HTH • HLH • Zn Finger • Alpha-helix

19. Control of gene expression • Binding of conserved motifs to double helix

21. Control of gene expression • Steroid receptors and response elements • GR • ER • PR • RAR • TR • VDR

23. Control of gene expression • Transcription regulation by glucocorticoids

25. Control of gene expression • Target gene expression via signal transduction • Protein kinase: hormonal signaling through cAMP-pt kinase A pathway • Cytoplasmic transcription factor NF kappa B and translocation to the nucleus

28. Control of gene expression • Major Classes of Cell Surface Receptor • G protein coupled • Serine-Threonine kinase • Tyrosine kinase • Tyrosine kinase associated JAK (janus protein kinase) activity in JAK-STAT signaling • Ion channel-linked

29. Control of gene expression • Secondary Messengers in Cell Signaling • Cyclic AMP (cAMP) • Cyclic GMP (cGMP) • Phospholipids/Ca

30. Control of gene expression • The IRE binding protein and iron-response elements (IREs)

32. Control of gene expression • Genes with multiple promoters • Dystrophin has eight promoters

34. Control of gene expression • Differential RNA splicing • Wt1 Wilm’s tumor (four splice forms) • Calcitonin gene (tissue specific products)

38. Control of gene expression • Tissue specific RNA editing • Apolipoprotein B gene (rare)

40. Control of gene expression • Methylation and gene expression • Largely confined to CpG dinucleotides • CpG islands • Methylation patterns change during development • Sex-specific regulation

42. Control of gene expression • Methylation • CpG islands

44. Control of gene expression • Methylation • Changes in methylation throughout development

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47. Control of gene expression • Methylation • Sex-specific regulation of the Dnmt1 methyl transferase gene • 1so somatic • 1sp spermatocytes • 1oo oocytes

49. Control of gene expression • Transcriptional repression by histone deacetylation • Mediated by methylation • Methylated CpG’s bound by MeCP2 repressor