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Chromatin remodeling ATPases non-covalent change

Chromatin remodeling ATPases non-covalent change. Lecture outline. Types of chromatin remodelers complexes protein domains Activities of chromatin remodelers on chromatin in the organism. Chromatin remodeling ATPases. txn assembly. DNA methylation. txn. exchange. txn repression.

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Chromatin remodeling ATPases non-covalent change

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  1. Chromatin remodeling ATPases non-covalent change

  2. Lecture outline Types of chromatin remodelers complexes protein domains Activities of chromatin remodelers on chromatin in the organism

  3. Chromatin remodeling ATPases txn assembly DNA methylation txn exchange txn repression repair DNA methylation heterochromation recombination archeal TBP

  4. ISWI CHD SWI2/SNF2 INO80/SWR1

  5. ATPase domain Clapier and Cairns Ann. Rev. Biochem. 2009

  6. Activities of chromatin remodeling ATPases

  7. Chromatin assembly Clapier and Cairns, Annu. Rev. Biochem. 2009

  8. Dynamic Range of Chromatin Structure Created by ATP-Dependent Chromatin Remodeling Slide courtesy of Dr. Hua-Ying Fan

  9. Shared characteristics of chromatin remodeling • complexes • bind nucleosomes • are DNA-dependent ATPases • recognize histone modifications • ATPase activity can be regulated • interact with other proteins From Clapier and Cairns, Annu. Rev. Biochem. 2009

  10. Assays for chromatin remodeling Non-covalent alteration!

  11. sliding

  12. Assays for chromatin remodeling Also MNAse qPCR or MNAse seq or MNAse H3 ChIP seq

  13. Persistence

  14. Proc. Natl. Acad. Sci. USA Vol. 95, pp. 4947–4952, April 1998 Perturbation of nucleosome core structure by the SWI/SNF complex persists after its detachment, enhancing subsequent transcription factor binding JACQUES COˆTE ,CRAIG L. PETERSON, AND JERRY L. WORKMAN cold competitor oligonucleosomes

  15. Chromatin remodeling one remodeler per nucleosome multiple enzymatic reactions destabilize 1 nucleosome 14 histone-DNA contacts use ATP hydrolysis to break (ca. 1kcal/mol for each contact) ATPases bind near center of nucleosomes (2 turns from dyad) translocate along DNA 3’ to 5’ generate DNA loops, reposition nucleosome or destabilize

  16. ISWI (SNF2H)

  17. SMALL COMPLEXES (generally) Yadon and Tsukiyama Cell Snapshot 2011

  18. SMALL COMPLEXES (generally) MANY COMPLEXES Yadon and Tsukiyama

  19. Roles of ISWI nucleosome array formation chromatin assembly, replication heterochromatin formation reprogramming (nuclear transfer) transcriptional regulation some PolII, PolI

  20. ISWI can position nucleosomes onto unfavorable DNA

  21. ISWI role in transcription ISWI: green PolII: red Deuring et al., Molecular Cell, Vol. 5, 355–365, February, 2000The ISWI Chromatin-Remodeling Protein Is Required for Gene Expression and the Maintenance of Higher Order Chromatin Structure In Vivo.

  22. ISWI: required for condensation of male X Female iswi mut. Male iswi mut. Deuring et al., Molecular Cell, Vol. 5, 355–365, February, 2000The ISWI Chromatin-Remodeling Protein Is Required for Gene Expression and the Maintenance of Higher Order Chromatin Structure In Vivo.

  23. Role of the domains

  24. Role of the domains Blue + charge Red - charge

  25. Role of the domains Yamada et al., Nature 2011

  26. ROLE of ISWI domains SANT/HAND domain contacts histone tails - charge: histone tail interaction + charge: DNA interaction Slide domain linker DNA contact, ’measures’ distance equal spacing of nucleosomes ATPase domain near dyad, motor, translocation

  27. Loop propagation models Yamada et al., Nature 2011

  28. SWI/SNF

  29. SWI2/SNF2 subfamily of chromatin-remodeling ATPases Isolated as sucrose-non-fermenting mutants in yeast snf2, snf5, snf6 Isolated as mating type switch deficient mutants in yeast swi1, swi2, swi3 SNF2=SWI2

  30. LARGE COMPLEXES (generally) Ca. 11 subunits, 2 MD in size Casten et al., Cell snapshot 2011

  31. SWI2/SNF2 complexes Core complex ATPaseSnf2 (BRM/BRG1) Snf5 (BAF47) Swi3 (BAF155/BAF170) Function of some subunits not yet understood ATPase and core: sufficient in vitro, other subunits required in vivo other subunits Swp73 or BAF60 actin related proteins (ARP) BAF 57

  32. Two types of complexes in most organisms a,b a,b Trends in Genetics 2007

  33. Clapier and Cairns, Annu. Rev. Biochem. 2009

  34. Ho and Crabtree Nature 2010

  35. ROLE of SNF2/BRM domains BROMO domain binds acetylated lysines on histone tails HSA domain protein interactions actin/ARP transcription factors ATPase domain near dyad, motor, translocation

  36. ROLE of SNF2/BRM domains Hopfner et al. COSB 2012 Sen et al., NAR 2011 New SnAC domain required for remodeling activity

  37. SNF2 ATPase activity change nucleosome position increased regulatory protein access! change nucleosome conformation eject histone octamer displace H2A/H2B dimer

  38. Roles of SWI2/SNF2 Inducible gene expression: transcription initiation transcription elongation Splicing Repair Roles in development and stress responses

  39. Activation or repression! sliding ATP-dependent Chromatin Remodeling Complex Cis-regulatory element

  40. Activation or repression! sliding ATP-dependent Chromatin Remodeling Complex Cis-regulatory element

  41. Only a subset of genes depends on SWI2/SNF2 Holstege et al. (1998) Cell 95 Whole genome expression analysis in S. cerevisiae

  42. SWI2/SNF2 activities Role in activation and repression of transcription Regulation of select genes

  43. Proc. Natl. Acad. Sci. USA Vol. 95, pp. 4947–4952, April 1998 Perturbation of nucleosome core structure by the SWI/SNF complex persists after its detachment, enhancing subsequent transcription factor binding JACQUES COˆTE ,CRAIG L. PETERSON, AND JERRY L. WORKMAN cold competitor oligonucleosomes

  44. The 2MD SWI/SNF complex fits around the entire nucleosome Zhang et al.

  45. Nature Structural & Molecular Biology 15, 1272 - 1277 (2008) Published online: 23 November 2008 http://www.nature.com/nsmb/journal/v15/n12/extref/nsmb.1524-S5.mov

  46. RSC docks onto nucleosome 1 = ATPase

  47. Casten et al., Cell snapshot 2011

  48. Liu et al., MCB2011

  49. CHD ATPases CHD1: role in chromatin assembly; open chromatin in pluripotent cells CHD3, 4 HDAC complex subunits! NuRD complex also contains Me-DNA binding protein (MBD2) complex connects deacetylation, chromatin remodeling and DNA methylation; repressive function CHD7: together with PBAF; CHARGE syndrome Together with SNF2: role in transcriptional elongation

  50. Sims and Wade, Cell Snapshot 2011

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