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Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development

Author

Listed:
  • Hank H. Qi

    (Harvard Medical School
    Children’s Hospital)

  • Madathia Sarkissian

    (Dana Farber Cancer Institute
    Present addresses: Constellation Pharmaceuticals, 148 Sidney Street, Cambridge, Massachusetts 02139, USA (M.S.; F.L.); Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA (M.H.); Department of Biology, Texas A&M University, College Station, Texas 77843, USA (N.K.Y.).)

  • Gang-Qing Hu

    (Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Zhibin Wang

    (Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Arindam Bhattacharjee

    (Agilent Technologies)

  • D. Benjamin Gordon

    (Agilent Technologies)

  • Michelle Gonzales

    (Princeton University)

  • Fei Lan

    (Harvard Medical School
    Present addresses: Constellation Pharmaceuticals, 148 Sidney Street, Cambridge, Massachusetts 02139, USA (M.S.; F.L.); Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA (M.H.); Department of Biology, Texas A&M University, College Station, Texas 77843, USA (N.K.Y.).)

  • Pat P. Ongusaha

    (Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School)

  • Maite Huarte

    (Harvard Medical School
    Present addresses: Constellation Pharmaceuticals, 148 Sidney Street, Cambridge, Massachusetts 02139, USA (M.S.; F.L.); Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA (M.H.); Department of Biology, Texas A&M University, College Station, Texas 77843, USA (N.K.Y.).)

  • Nasser K. Yaghi

    (Harvard Medical School
    Present addresses: Constellation Pharmaceuticals, 148 Sidney Street, Cambridge, Massachusetts 02139, USA (M.S.; F.L.); Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA (M.H.); Department of Biology, Texas A&M University, College Station, Texas 77843, USA (N.K.Y.).)

  • Huijun Lim

    (Harvard Medical School
    Children’s Hospital)

  • Benjamin A. Garcia

    (Princeton University)

  • Leonardo Brizuela

    (Agilent Technologies)

  • Keji Zhao

    (Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Thomas M. Roberts

    (Dana Farber Cancer Institute)

  • Yang Shi

    (Harvard Medical School
    Children’s Hospital)

Abstract

Histone demethylase activity of PHF8 Mutations in the PHF8 gene, which encodes the plant homeo domain (PHD) finger protein 8, are connected to X-linked mental retardation associated with cleft lip and cleft palate. Two groups now report that the PHF8 protein is a histone demethylase with activity against H4K20me1 (histone H4 lysine 20). Qi et al. report a role for PHF8 in regulating gene expression, as well as in neuronal cell survival and craniofacial development in zebrafish. The results suggest there may be a link between histone methylation dynamics and X-linked mental retardation. Liu et al. show that PHF8 is linked to two distinct events during cell-cycle progression. PHF8 is recruited to the promoters of G1/S-phase genes where it removes H4K20me1 and contributes to gene activation, whereas dissociation of PHF8 from chromatin in prophase allows H4K20me1 to accumulate during mitosis.

Suggested Citation

  • Hank H. Qi & Madathia Sarkissian & Gang-Qing Hu & Zhibin Wang & Arindam Bhattacharjee & D. Benjamin Gordon & Michelle Gonzales & Fei Lan & Pat P. Ongusaha & Maite Huarte & Nasser K. Yaghi & Huijun Lim, 2010. "Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development," Nature, Nature, vol. 466(7305), pages 503-507, July.
    • Handle: RePEc:nat:nature:v:466:y:2010:i:7305:d:10.1038_nature09261
    DOI: 10.1038/nature09261
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