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Role of histone H2A ubiquitination in Polycomb silencing

Naturevolume 431, pages873–878 (2004)Cite this article

Abstract

Covalent modification of histones is important in regulating chromatin dynamics and transcription1,2. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B3. Although recent studies have uncovered the enzymes involved in histone H2B ubiquitination4,5,6 and a ‘cross-talk’ between H2B ubiquitination and histone methylation7,8, 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 theDrosophila 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 ofUbx. Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing.

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Figure 1: Identification of an H2A ubiquitin ligase activity in HeLa cells.
Figure 2: Purification and identification of the H2A ubiquitination ligase complex.
Figure 3: Ring2 is the catalytic subunit and is required for H2A ubiquitinationin vivo.
Figure 4: dRing-dependent H2A ubiquitination atUbx PRE and promoter regions.

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References

  1. Jenuwein, T. & Allis, C. D. Translating the histone code.Science293, 1074–1080 (2001)

    Article CAS  Google Scholar 

  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)

    Article CAS  Google Scholar 

  3. Zhang, Y. Transcriptional regulation by histone ubiquitination and deubiquitination.Genes Dev.17, 2733–2740 (2003)

    Article CAS  Google Scholar 

  4. Robzyk, K., Recht, J. & Osley, M. A. Rad6-dependent ubiquitination of histone H2B in yeast.Science287, 501–504 (2000)

    Article ADS CAS  Google Scholar 

  5. Hwang, W. W. et al. A conserved RING finger protein required for histone H2B monoubiquitination and cell size control.Mol. Cell11, 261–266 (2003)

    Article CAS  Google Scholar 

  6. Wood, A. et al. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter.Mol. Cell11, 267–274 (2003)

    Article CAS  Google Scholar 

  7. Sun, Z. W. & Allis, C. D. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast.Nature418, 104–108 (2002)

    Article ADS CAS  Google Scholar 

  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)

    Article CAS  Google Scholar 

  9. Nickel, B. E. & Davie, J. R. Structure of polyubiquitinated histone H2A.Biochemistry28, 964–968 (1989)

    Article CAS  Google Scholar 

  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)

    Article ADS CAS  Google Scholar 

  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)

    Article CAS  Google Scholar 

  12. Fritsch, C., Beuchle, D. & Muller, J. Molecular and genetic analysis of the Polycomb group gene Sex combs extra/Ring inDrosophila.Mech. Dev.120, 949–954 (2003)

    Article CAS  Google Scholar 

  13. Gorfinkiel, N. et al. TheDrosophila Polycomb group gene Sex combs extra encodes the ortholog of mammalian Ring1 proteins.Mech. Dev.121, 449–462 (2004)

    Article CAS  Google Scholar 

  14. Francis, N. J., Saurin, A. J., Shao, Z. & Kingston, R. E. Reconstitution of a functional core polycomb repressive complex.Mol. Cell8, 545–556 (2001)

    Article CAS  Google Scholar 

  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)

    Article CAS  Google Scholar 

  16. Joazeiro, C. A. & Weissman, A. M. RING finger proteins: mediators of ubiquitin ligase activity.Cell102, 549–552 (2000)

    Article CAS  Google Scholar 

  17. Wang, H. et al. mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression.Mol. Cell12, 475–487 (2003)

    Article CAS  Google Scholar 

  18. 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)

    CAS PubMed  Google Scholar 

  19. Cao, R. & Zhang, Y. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex.Mol. Cell15, 57–67 (2004)

    Article CAS  Google Scholar 

  20. Voncken, J. W. et al. Rnf2 (Ring1b) deficiency causes gastrulation arrest and cell cycle inhibition.Proc. Natl Acad. Sci. USA100, 2468–2473 (2003)

    Article ADS CAS  Google Scholar 

  21. Cao, R. et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing.Science298, 1039–1043 (2002)

    Article ADS CAS  Google Scholar 

  22. Wang, L. et al. Hierarchical recruitment of polycomb group silencing complexes.Mol. Cell14, 637–646 (2004)

    Article MathSciNet CAS  Google Scholar 

  23. Henry, K. W. et al. Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8.Genes Dev.17, 2648–2663 (2003)

    Article CAS  Google Scholar 

  24. Kao, C. F. et al. Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B.Genes Dev.18, 184–195 (2004)

    Article CAS  Google Scholar 

  25. 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)

    Article CAS  Google Scholar 

  26. Briggs, S. D. et al. Gene silencing: trans-histone regulatory pathway in chromatin.Nature418, 498 (2002)

    Article ADS CAS  Google Scholar 

  27. 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)

    Article CAS  Google Scholar 

  28. Plath, K. et al. Role of histone H3 lysine 27 methylation in X inactivation.Science300, 131–135 (2003)

    Article ADS CAS  Google Scholar 

  29. 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)

    Article CAS  Google Scholar 

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Acknowledgements

We thank J. Kim for help with mass spectrometry. This work was supported by NIH grants to Y.Z., R.S.J. and P.T.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7295, USA

    Hengbin Wang & Yi Zhang

  2. Department of Biological Sciences, Southern Methodist University, Dallas, Texas, 75275, USA

    Liangjun Wang & Richard S. Jones

  3. Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10021, New York, USA

    Hediye Erdjument-Bromage & Paul Tempst

  4. Departmamento de Desarrollo y Biologia Celular, Centro de Investigaciones Biologicas, Ramiro de Maeztu, 9, E28040, Madrid, Spain

    Miguel Vidal

Authors
  1. Hengbin Wang
  2. Liangjun Wang
  3. Hediye Erdjument-Bromage
  4. Miguel Vidal
  5. Paul Tempst
  6. Richard S. Jones
  7. Yi Zhang

Corresponding author

Correspondence toYi Zhang.

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Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Data

The monoclonal uH2A antibody recognizes uH2A from Drosophila SL2 cells. (DOC 113 kb)

Supplementary Methods

Purification and identification of histone H2A ubiquitin ligase complex. 2. Generation and characterization of Ring2 knock-down cell lines. 3. Extraction of ubiquitinated histones from Drosophila SL2 cells. (DOC 53 kb)

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Wang, H., Wang, L., Erdjument-Bromage, H.et al. Role of histone H2A ubiquitination in Polycomb silencing.Nature431, 873–878 (2004). https://doi.org/10.1038/nature02985

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