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Rb targets histone H3 methylation and HP1 to promoters

Nature volume 412, pages 561–565 (2001)Cite this article

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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Figure 1: Rb interacts with methylase activity specific for H3 Lys 9.
Figure 2: SUV39H1 and Rb interact and regulate transcription.
Figure 3: HP1 interacts with Rb in an LXCXE-dependent fashion.
Figure 4: Rb is required for HP1 promoter recruitment.
Figure 5: Role of the SUV39H1–HP1 complex in the transcriptional co-repressor function of Rb.

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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

  1. Soren J. Nielsen, Robert Schneider, Ron Firestein and Michael Cleary: These authors have contributed equally to this work.

Authors and Affiliations

  1. 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

  2. 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

  3. Research Institute of Molecular Pathology (IMP), The Vienna Biocenter, Dr. Bohrgasse 7, Vienna, A-1030, Austria

    Donal O'Carroll & Thomas Jenuwein

  4. Department of Pathology, Stanford University Medical Center, Stanford, 94305, California, USA

    Ron Firestein & Michael Cleary

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  1. Soren J. Nielsen
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Correspondence to Tony 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

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