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1. Intro slide
2. E1A oncoprotein targets
3. CtBP domain structure
4. CtBP binding proteins
5. CtBP repression model
6. Purification of a CtBP complex
7. Enzymatic activities in the CtBP complex
8. Methylation is important for silencing
9. Coordinated histone modifications by CtBP
10. Deacetylation and methylation by CtBP
11. E-cadherin function and regulation
12. Inhibition of CtBP de-represses E-cad promoter
13. Histone modifications at the E-cad promoter
14. Improved CtBP repression model
15. CtBP mechanism of action-further questions
16. LSD1 is present in multiple repressor complexes
17. LSD1 domain structure
18. LSD1 is evolutionarily conserved
19. LSD1 is a transcriptional co-repressor
20. The amine oxidase is required for repressor activity
21. Possible substrates for amine oxidases
22. Models for histone methylation regulation
23. Demethylation reaction mediated by LSD1
24. Sites to be considered
25. LSD1 demethylates diMeK4H3 but not diMeK9H4
26. Native diMeK4H3 is the substrate of LSD1
27. Endogenous LSD1 also demethylates diMeK4H3
28. Specificity of LSD1
29. Demethylation reaction mediated by LSD1
30. Mass spec. identifies unmodified H3 peptide
31. Demethylation reaction mediated by LSD1
32. Formaldehyde dehydrogenase assay (FDH assay)
33. Formaldehyde - product of demethylation reaction
34. ESI-LC-MS identifies formaldehyde
35. De-repression of genes in LSD1 RNAi cell
36. K4 methylation - LSD1 occupancy correlation
37. Summary
38. Conclusions
39. Demethylation regulation
40. LSD1 associated factors
41. Co-REST restores LSD1 activity on nucleosomes
42. Co-REST stimulatory activity mapping
43. Co-REST regulates LSD1 stability in vivo
44. Co-REST regulates LSD1 promoter occupancy
45. The SANT domain
46. LSD1/Co-REST prefer hypoacetylated histones
47. BHC80 inhibits LSD1 demethylation in vitro
48. Summary
49. A model
50. Acknowledgements

Topics Covered

• Mechanisms of transcriptional repression
• Corepressor proteins
• Histone modifications involved in repression
• Cancer

Links

Series:

• Eukaryotic Gene Regulation

Categories:

• Cancer
• Cell Biology
• Genetics & Epigenetics

Therapeutic Areas:

• Oncology

Talk Citation

Publication History

• Published on October 1, 2007
• Archived on July 23, 2015

Financial Disclosures

• Dr. Yang Shi has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.