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Role of histone H2A ubiquitination in Polycomb silencing

Wang, Hengbin, Wang, Liangjun, Erdjument-Bromage, Hediye, Vidal, Miguel, Tempst, Paul, Jones, Richard S., Zhang, Yi·2004·Nature
DOI 10.1038/nature02985
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Abstract

Covalent modification of histones is important in regulating chromatin dynamics and transcription. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B. Although recent studies have uncovered the enzymes involved in histone H2B ubiquitination and a 'cross-talk' between H2B ubiquitination and histone methylation, the responsible enzymes and the functions of H2A ubiquitination are unknown. Here we report the purification and functional characterization of an E3 ubiquitin ligase complex that is specific for histone H2A. The complex, termed hPRC1L (human Polycomb repressive complex 1-like), is composed of several Polycomb-group proteins including Ring1, Ring2, Bmi1 and HPH2. hPRC1L monoubiquitinates nucleosomal histone H2A at lysine 119. Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. Chromatin immunoprecipitation analysis demonstrated colocalization of dRing with ubiquitinated H2A at the PRE and promoter regions of the Drosophila Ubx gene in wing imaginal discs. Removal of dRing in SL2 tissue culture cells by RNA interference resulted in loss of H2A ubiquitination concomitant with derepression of Ubx. Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing.

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Crossref · 10.1038/nature02985

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Citations

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Research works printed but not linked: 26

  1. Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001) · DOI · Paper page
  2. Zhang, Y. & Reinberg, D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 15, 2343–2360 (2001) · DOI
  3. Zhang, Y. Transcriptional regulation by histone ubiquitination and deubiquitination. Genes Dev. 17, 2733–2740 (2003) · DOI
  4. Robzyk, K., Recht, J. & Osley, M. A. Rad6-dependent ubiquitination of histone H2B in yeast. Science 287, 501–504 (2000) · DOI
  5. Hwang, W. W. et al. A conserved RING finger protein required for histone H2B monoubiquitination and cell size control. Mol. Cell 11, 261–266 (2003) · DOI
  6. Wood, A. et al. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol. Cell 11, 267–274 (2003) · DOI
  7. Sun, Z. W. & Allis, C. D. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418, 104–108 (2002) · DOI
  8. Dover, J. et al. Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6. J. Biol. Chem. 277, 28368–28371 (2002) · DOI
  9. Nickel, B. E. & Davie, J. R. Structure of polyubiquitinated histone H2A. Biochemistry 28, 964–968 (1989) · DOI
  10. Lee, S. J. et al. E3 ligase activity of RING finger proteins that interact with Hip-2, a human ubiquitin-conjugating enzyme. FEBS Lett. 503, 61–64 (2001) · DOI
  11. Satijn, D. P. et al. RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor. Mol. Cell. Biol. 17, 4105–4113 (1997) · DOI
  12. Fritsch, C., Beuchle, D. & Muller, J. Molecular and genetic analysis of the Polycomb group gene Sex combs extra/Ring in Drosophila. Mech. Dev. 120, 949–954 (2003) · DOI
  13. Gorfinkiel, N. et al. The Drosophila Polycomb group gene Sex combs extra encodes the ortholog of mammalian Ring1 proteins. Mech. Dev. 121, 449–462 (2004) · DOI
  14. Francis, N. J., Saurin, A. J., Shao, Z. & Kingston, R. E. Reconstitution of a functional core polycomb repressive complex. Mol. Cell 8, 545–556 (2001) · DOI
  15. Levine, S. S. et al. The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans. Mol. Cell. Biol. 22, 6070–6078 (2002) · DOI
  16. Wang, H. et al. mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression. Mol. Cell 12, 475–487 (2003) · DOI
  17. Vassilev, A. P., Rasmussen, H. H., Christensen, E. I., Nielsen, S. & Celis, J. E. The levels of ubiquitinated histone H2A are highly upregulated in transformed human cells: partial colocalization of uH2A clusters and PCNA/cyclin foci in a fraction of cells in S-phase. J. Cell Sci. 108, 1205–1215 (1995) · DOI
  18. Cao, R. & Zhang, Y. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Mol. Cell 15, 57–67 (2004) · DOI
  19. Voncken, J. W. et al. Rnf2 (Ring1b) deficiency causes gastrulation arrest and cell cycle inhibition. Proc. Natl Acad. Sci. USA 100, 2468–2473 (2003) · DOI
  20. Wang, L. et al. Hierarchical recruitment of polycomb group silencing complexes. Mol. Cell 14, 637–646 (2004) · DOI
  21. Kao, C. F. et al. Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B. Genes Dev. 18, 184–195 (2004) · DOI
  22. Ng, H. H., Xu, R. M., Zhang, Y. & Struhl, K. Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79. J. Biol. Chem. 277, 34655–34657 (2002) · DOI
  23. Briggs, S. D. et al. Gene silencing: trans-histone regulatory pathway in chromatin. Nature 418, 498 (2002) · DOI
  24. Devroe, E., Erdjument-Bromage, H., Tempst, P. & Silver, P. A. Human Mob proteins regulate the NDR1 and NDR2 serine-threonine kinases. J. Biol. Chem. 279, 24444–24451 (2004) · DOI
  25. Plath, K. et al. Role of histone H3 lysine 27 methylation in X inactivation. Science 300, 131–135 (2003) · DOI
  26. Schoorlemmer, J. et al. Ring1A is a transcriptional repressor that interacts with the Polycomb-M33 protein and is expressed at rhombomere boundaries in the mouse hindbrain. EMBO J. 16, 5930–5942 (1997) · DOI

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Metadata

Authors
Wang, H., Wang, L., Erdjument-Bromage, H., Vidal, M., Tempst, P., Jones, R. S., & Zhang, Y.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2004-09-22
Volume
431
Issue
7010
Pages
873-878
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/nature02985
Cited by
1,663
References
3
Language
en
Licence
www.springer.com/tdm (tdm)

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