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HP1-mediated silencing targets Pol II coactivator complexes

Nature Structural & Molecular Biology volume 15, pages 318–320 (2008)Cite this article

Abstract

Little is known of the specific biochemical mechanism by which heterochromatin protein 1 (HP1) inactivates a gene. We analyzed HP1-mediated inhibition of preinitiation complex (PIC) assembly in vitro on chromatin templates regulated by GAL4-VP16 or Sp1. HP1 blocked key subunits of the TFIID and Mediator coactivator complexes. Notably, binding of the same subunits was inhibited by HP1 on the Sp1-regulated survivin gene in vivo upon DNA damage–induced silencing.

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Figure 1: Heterochromatin protein 1 (HP1) blocks formation of a full preinitiation complex (PIC) and represses transcription.
Figure 2: Effect on purified DAMed complex.
Figure 3: Heterochromatin protein 1 (HP1) inhibits preinitiation complex (PIC) formation on the survivin promoter in vitro and in vivo.

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Acknowledgements

This study was supported by a grant from the US National Institutes of Health to M.C. (GM074701). J.C.B. was supported by a Ruth L. Kirschstein National Research Award (GM07185). We thank S. Smale (University of California, Los Angeles) for HP1 antibodies, and J. Conaway and R. Conaway (Stowers Institute for Medical Research, Kansas City, Missouri, USA) for the MED4 antibody.

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Author notes

  1. Andrea Smallwood and Joshua C Black: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Chemistry, 351A Biomedical Sciences Research Building, David Geffen School of Medicine, University of California, Los Angeles, 90095-1737, California, USA

    Andrea Smallwood, Joshua C Black & Michael Carey

  2. Department of Microbiology, 550 First Avenue, New York University School of Medicine, New York, 10016, New York, USA

    Naoko Tanese

  3. New England Biolabs, 240 County Road, Ipswich, 01938, Massachusetts, USA

    Sriharsa Pradhan

Authors
  1. Andrea Smallwood
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  2. Joshua C Black
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  3. Naoko Tanese
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  4. Sriharsa Pradhan
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  5. Michael Carey
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Contributions

A.S. and J.C.B. designed and performed the experiments and prepared the manuscript; N.T. and S.P. contributed reagents and assisted with experimental design; M.C. designed experiments, analyzed data and prepared the manuscript.

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Correspondence to Michael Carey.

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Smallwood, A., Black, J., Tanese, N. et al. HP1-mediated silencing targets Pol II coactivator complexes. Nat Struct Mol Biol 15, 318–320 (2008). https://doi.org/10.1038/nsmb.1385

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