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

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, Benjamin A. Garcia, Leonardo Brizuela, Keji Zhao, Thomas M. Roberts () and Yang Shi ()
Additional contact information
Hank H. Qi: Harvard Medical School
Madathia Sarkissian: Dana Farber Cancer Institute
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
Pat P. Ongusaha: Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School
Maite Huarte: Harvard Medical School
Nasser K. Yaghi: Harvard Medical School
Huijun Lim: Harvard Medical School
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

Nature, 2010, vol. 466, issue 7305, 503-507

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.

Date: 2010
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DOI: 10.1038/nature09261

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