Rb targets histone H3 methylation and HP1 to promoters (original) (raw)
- Letter
- Published: 01 August 2001
- Robert Schneider1 na1,
- Uta-Maria Bauer1,
- Andrew J. Bannister1,
- Ashby Morrison2,
- Donal O'Carroll3,
- Ron Firestein4 na1,
- Michael Cleary4 na1,
- Thomas Jenuwein3,
- Rafael E. Herrera2 &
- …
- Tony Kouzarides1
Nature volume 412, pages 561–565 (2001)Cite this article
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Abstract
In eukaryotic cells the histone methylase SUV39H1 and the methyl-lysine binding protein HP1 functionally interact to repress transcription at heterochromatic sites1. Lysine 9 of histone H3 is methylated by SUV39H1 (ref. 2), creating a binding site for the chromo domain of HP1 (refs 3, 4). Here we show that SUV39H1 and HP1 are both involved in the repressive functions of the retinoblastoma (Rb) protein. Rb associates with SUV39H1 and HP1 in vivo by means of its pocket domain. SUV39H1 cooperates with Rb to repress the cyclin E promoter, and in fibroblasts that are disrupted for SUV39, the activity of the cyclin E and cyclin A2 genes are specifically elevated. Chromatin immunoprecipitations show that Rb is necessary to direct methylation of histone H3, and is necessary for binding of HP1 to the cyclin E promoter. These results indicate that the SUV39H1–HP1 complex is not only involved in heterochromatic silencing but also has a role in repression of euchromatic genes by Rb and perhaps other co-repressor proteins.
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References
- Jones, D. O., Cowell, I. G. & Singh, P. B. Mammalian chromodomain proteins: their role in genome organisation and expression. BioEssays 22, 124–137 (2000).
Article CAS Google Scholar - Rea, S. et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593–599 (2000).
Article ADS CAS Google Scholar - Bannister, A. J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120–124 (2001).
Article ADS CAS Google Scholar - Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 120–124 (2001).
Article ADS Google Scholar - Brehm, A. et al. Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391, 597–601 (1998).
Article ADS CAS Google Scholar - Magnaghi-Jaulin, L. et al. Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature 391, 601–605 (1998).
Article ADS CAS Google Scholar - Luo, R. X., Postigo, A. A. & Dean, D. C. Rb interacts with histone deacetylase to repress transcription. Cell 92, 463–473 (1998).
Article CAS Google Scholar - Firestein, R., Cui, X., Huie, P. & Cleary, M. L. Set domain-dependent regulation of transcriptional silencing and growth control by SUV39H1, a mammalian ortholog of Drosophila Su(var)3-9. Mol. Cell. Biol. 20, 4900–4909 (2000).
Article CAS Google Scholar - Hurford, R. K. Jr, Cobrinik, D., Lee, M. & Dyson, N. pRB and p107/p130 are required for regulated expression of different sets of E2F responsive genes. Genes Dev. 11, 1447–1463 (1997).
Article CAS Google Scholar - Herrera, R. E. et al. Altered cell cycle kinetics, gene expression and G1 restriction point regulation in Rb deficient fibroblasts. Mol. Cell. Biol. 16, 2402–2407 (1996).
Article CAS Google Scholar - Aagaard, L. et al. Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31. EMBO J. 18, 1923–1938 (1999).
Article CAS Google Scholar - Williams, L. & Grafi, G. The retinoblastoma protein—a bridge to heterochromatin. Trends Plant Sci. 5, 239–240 (2000).
Article CAS Google Scholar - Korner, K. & Muller, R. J. In vivo structure of the cell cycle-regulated human cdc25C promoter. Biol. Chem. 275, 18676–18681 (2000).
Article CAS Google Scholar - Hagemeier, C., Cook, A. & Kouzarides, T. The retinoblastoma protein binds E2F residues required for activation in vivo and TBP binding in vitro. Nucleic Acids Res. 21, 4998–5004 (1993).
Article CAS Google Scholar - Qin, X. Q., Chittenden, T., Livingston, D. M. & Kaelin, W. G. Jr Identification of a growth suppression domain within the retinoblastoma gene product. Genes Dev. 6, 953–964 (1992).
Article CAS Google Scholar - Bannister, A. J. & Kouzarides, T. The CBP co-activator is a histone acetyltransferase. Nature 384, 641–643 (1996).
Article ADS CAS Google Scholar - Nielsen, A. L. et al. Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family. EMBO J. 18, 6385–6395 (1999).
Article CAS Google Scholar - Orlando, V., Strutt, H. & Paro, R. Analysis of chromatin structure by in vivo formaldehyde cross-linking. Methods 11, 205–214 (1997).
Article CAS Google Scholar - Dedon, P. C., Soults, J. A., Allis, C. D. & Gorovsky, M. A. A simplified formaldehyde fixation and immunopreciptation technique for studying protein–DNA interactions. Anal. Biochem. 197, 83–90 (1991).
Article CAS Google Scholar
Acknowledgements
We thank M. Weldon for Edman degradation of labelled proteins; H. Herschman for providing GAR; R. Laskey for the anti-HP1 antibody; and A. Cook for technical assistance. S.J.N. and A.J.B. were funded by a grant from the Cancer Research Campaign, R.S. by an EC grant and an EMBO fellowship, and U.M.B. by an HFSP grant.
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Author notes
- Soren J. Nielsen, Robert Schneider, Ron Firestein and Michael Cleary: These authors have contributed equally to this work.
Authors and Affiliations
- Wellcome/CRC Institute and Department of Pathology, Tennis Court Road, Cambridge, CB2 1QR, UK
Soren J. Nielsen, Robert Schneider, Uta-Maria Bauer, Andrew J. Bannister & Tony Kouzarides - Department of Molecular and Cellular Biology, Baylor College of Medicine, The Breast Center, 1 Baylor Plaza, Houston, 77030, Texas, USA
Ashby Morrison & Rafael E. Herrera - Research Institute of Molecular Pathology (IMP), The Vienna Biocenter, Dr. Bohrgasse 7, Vienna, A-1030, Austria
Donal O'Carroll & Thomas Jenuwein - Department of Pathology, Stanford University Medical Center, Stanford, 94305, California, USA
Ron Firestein & Michael Cleary
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Correspondence toTony Kouzarides.
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Nielsen, S., Schneider, R., Bauer, UM. et al. Rb targets histone H3 methylation and HP1 to promoters.Nature 412, 561–565 (2001). https://doi.org/10.1038/35087620
- Received: 06 April 2001
- Accepted: 06 July 2001
- Published: 01 August 2001
- Issue Date: 02 August 2001
- DOI: https://doi.org/10.1038/35087620