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The Polycomb Group Protein SUZ12 regulates histone H3 lysine 9 methylation and HP1α distribution

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Abstract

Regulation of histone methylation is critical for proper gene expression and chromosome function. Suppressor of Zeste 12 (SUZ12) is a requisite member of the EED/EZH2 histone methyltransferase complexes, and is required for full activity of these complexes in vitro. In mammals and flies, SUZ12/Su(z)12 is necessary for trimethylation of histone H3 on lysine 27 (H3K27me3) on facultative heterochromatin. However, Su(z)12 is unique among Polycomb Group Proteins in that Su(z)12 mutant flies exhibit gross defects in position effect variegation, suggesting a role for Su(z)12 in constitutive heterochromatin formation. We investigated the role of Suz12 in constitutive heterochromatin and discovered that Suz12 is required for histone H3 lysine 9 tri-methylation (H3K9me3) in differentiated but not undifferentiated mouse embryonic stem cells. Knockdown of SUZ12 in human cells caused a reduction in H3K27me3 and H3K9me3, and altered the distribution of HP1α. In contrast, EZH2 knockdown caused loss of H3K27me3 but not H3K9me3, indicating that SUZ12 regulates H3-K9 methylation in an EZH2-independent fashion. This work uncovers a role for SUZ12 in H3-K9 methylation.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, 94143, USA

    Cecile C. de la Cruz & Barbara Panning

  2. Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK

    Antonis Kirmizis

  3. Department of Chemistry, University of California, Berkeley, CA, 94720, USA

    Matthew D. Simon

  4. RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, 230-0045, Japan

    Kyo-ichi Isono & Haruhiko Koseki

  5. Genentech Hall, Room S372B, 600 16th Street, San Francisco, CA, 94143-2200 (94158 for courier delivery), USA

    Barbara Panning

Authors
  1. Cecile C. de la Cruz
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  2. Antonis Kirmizis
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  3. Matthew D. Simon
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  4. Kyo-ichi Isono
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  5. Haruhiko Koseki
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  6. Barbara Panning
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Correspondence to Barbara Panning.

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de la Cruz, C.C., Kirmizis, A., Simon, M.D. et al. The Polycomb Group Protein SUZ12 regulates histone H3 lysine 9 methylation and HP1α distribution. Chromosome Res 15, 299–314 (2007). https://doi.org/10.1007/s10577-007-1126-1

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  • DOI: https://doi.org/10.1007/s10577-007-1126-1

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