Article thumbnail

The C-Terminus of Histone H2B Is Involved in Chromatin Compaction Specifically at Telomeres, Independently of Its Monoubiquitylation at Lysine 123

By Chen-Yi Wang, Chia-Yin Hua, Hsiang-En Hsu, Chia-Ling Hsu, Hsin-Yi Tseng, Duncan E. Wright, Pang-Hung Hsu, Chih-Hung Jen, Chia-Yeh Lin, Meng-Ying Wu, Min-Daw Tsai and Cheng-Fu Kao


Telomeric heterochromatin assembly in budding yeast propagates through the association of Silent Information Regulator (SIR) proteins with nucleosomes, and the nucleosome array has been assumed to fold into a compacted structure. It is believed that the level of compaction and gene repression within heterochromatic regions can be modulated by histone modifications, such as acetylation of H3 lysine 56 and H4 lysine 16, and monoubiquitylation of H2B lysine 123. However, it remains unclear as to whether or not gene silencing is a direct consequence of the compaction of chromatin. Here, by investigating the role of the carboxy-terminus of histone H2B in heterochromatin formation, we identify that the disorderly compaction of chromatin induced by a mutation at H2B T122 specifically hinders telomeric heterochromatin formation. H2B T122 is positioned within the highly conserved AVTKY motif of the αC helix of H2B. Heterochromatin containing the T122E substitution in H2B remains inaccessible to ectopic dam methylase with dramatically increased mobility in sucrose gradients, indicating a compacted chromatin structure. Genetic studies indicate that this unique phenotype is independent of H2B K123 ubiquitylation and Sir4. In addition, using ChIP analysis, we demonstrate that telomere structure in the mutant is further disrupted by a defect in Sir2/Sir3 binding and the resulting invasion of euchromatic histone marks. Thus, we have revealed that the compaction of chromatin per se is not sufficient for heterochromatin formation. Instead, these results suggest that an appropriately arrayed chromatin mediated by H2B C-terminus is required for SIR binding and the subsequent formation of telomeric chromatin in yeast, thereby identifying an intrinsic property of the nucleosome that is required for the establishment of telomeric heterochromatin. This requirement is also likely to exist in higher eukaryotes, as the AVTKY motif of H2B is evolutionarily conserved

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2008). Analysis of cryo-electron microscopy images does not support the existence of 30-nm chromatin fibers in mitotic chromosomes in situ.
  2. (2002). Analysis of RGS proteins in Saccharomyces cerevisiae.
  3. (2005). Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NADdependent histone deacetylation.
  4. (2005). BUR kinase selectively regulates H3 K4 trimethylation and H2B ubiquitylation through recruitment of the PAF elongation complex.
  5. (2007). Chromatin modifications and their function.
  6. (2010). Chromatin structure: does the 30-nm fibre exist in vivo?
  7. (2002). Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing.
  8. (2001). Common themes in mechanisms of gene silencing.
  9. (2002). COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression.
  10. (2008). Compensatory interactions between Sir3p and the nucleosomal LRS surface imply their direct interaction.
  11. (2009). Comprehensive mapping of long-range interactions reveals folding principles of the human genome.
  12. (2003). Controlling the double helix.
  13. (2002). Dot1p modulates silencing in yeast by methylation of the nucleosome core.
  14. (2009). Electron spectroscopic imaging of the nuclear landscape.
  15. (2005). Epigenetic silencing mechanisms in budding yeast and fruit fly: different paths, same destinations.
  16. (1987). Four genes responsible for a position effect on expression from
  17. (1999). Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3–9 encode centromere-associated proteins which complex with the heterochromatin component M31.
  18. (2002). Gene silencing: trans-histone regulatory pathway in chromatin.
  19. (1990). Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae.
  20. (2002). Genome-wide histone modifications: gaining specificity by preventing promiscuity.
  21. (2006). Genome-wide patterns of histone modifications in yeast.
  22. (2010). Global chromatin architecture reflects pluripotency and lineage commitment in the early mouse embryo.
  23. (2003). Heterochromatin and epigenetic control of gene expression.
  24. (2004). Hif1 is a component of yeast histone acetyltransferase B, a complex mainly localized in the nucleus.
  25. (2007). Higher-order structures of chromatin: the elusive 30 nm fiber.
  26. (2010). Histone H2B Cterminal helix mediates trans-histone H3K4 methylation independent of H2B ubiquitination.
  27. (2009). Histone H3 N-terminus regulates higher order structure of yeast heterochromatin.
  28. (2011). Histone H4 lysine 12 acetylation regulates telomeric heterochromatin plasticity in Saccharomyces cerevisiae.
  29. (2006). Histone H4-K16 acetylation controls chromatin structure and protein interactions.
  30. (2011). Living without 30 nm chromatin fibers.
  31. (2005). Maintenance of low histone ubiquitylation by Ubp10 correlates with telomereproximal Sir2 association and gene silencing.
  32. (2008). Mapping in vivo chromatin interactions in yeast suggests an extended chromatin fiber with regional variation in compaction.
  33. (2005). Mechanism of transcriptional silencing in yeast.
  34. (2001). Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
  35. (1991). Modifiers of position effect are shared between telomeric and silent mating-type loci in S.
  36. (2005). Molecular biology: antagonizing the neighbours.
  37. (2002). Ordered nucleation and spreading of silenced chromatin in Saccharomyces cerevisiae.
  38. (2005). Peptide mass mapping of acetylated isoforms of histone H4 from mouse lymphosarcoma cells treated with histone deacetylase (HDACs) inhibitors.
  39. (1999). Preparation of yeast cells for confocal microscopy.
  40. (2004). Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B.
  41. (2000). Rad6-dependent ubiquitination of histone H2B in yeast.
  42. (2002). Rap1-Sir4 binding independent of other Sir, yKu, or histone interactions initiates the assembly of telomeric heterochromatin in yeast.
  43. (2009). Reconstitution of heterochromatin-dependent transcriptional gene silencing.
  44. (2007). Regulation of histone methylation by demethylimination and demethylation.
  45. (2007). Role of the conserved Sir3-BAH domain in nucleosome binding and silent chromatin assembly.
  46. (2001). Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
  47. (2005). Shilatifard A
  48. (2001). Silenced chromatin is permissive to activator binding and PIC recruitment.
  49. (2009). Silent chromatin at the middle and ends: lessons from yeasts.
  50. (2010). Silent information regulator 3: the Goldilocks of the silencing complex.
  51. (1997). SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast.
  52. (2002). Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin.
  53. (2006). Spreading of silent chromatin: inaction at a distance.
  54. (2002). Steps in assembly of silent chromatin in yeast: Sir3-independent binding of a Sir2/Sir4 complex to silencers and role for Sir2-dependent deacetylation.
  55. (2001). Telomere looping permits gene activation by a downstream UAS in yeast.
  56. (1992). Telomere-proximal DNA in Saccharomyces cerevisiae is refractory to methyltransferase activity in vivo.
  57. (1996). The clustering of telomeres and colocalization with
  58. (2004). The function of telomere clustering in yeast: the circe effect.
  59. (2009). The glucanosyltransferase Gas1 functions in transcriptional silencing.
  60. (2007). to regulate telomeric heterochromatin structure in yeast.
  61. (2002). Trans-tail histone modifications: wedge or bridge?
  62. (2003). Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8.
  63. (2002). Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418: 104–108. H2B T122E Hinders Telomeric Chromatin Formation PLoS
  64. (2005). Ubp10/Dot4p regulates the persistence of ubiquitinated histone H2B: distinct roles in telomeric silencing and general chromatin.