PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression

Wen Liu, Bogdan Tanasa, Oksana V. Tyurina, Tian Yuan Zhou, Reto Gassmann, Wei Ting Liu, Kenneth A. Ohgi, Chris Benner, Ivan Garcia-Bassets, Aneel K. Aggarwal, Arshad Desai, Pieter C. Dorrestein, Christopher K. Glass and Michael G. Rosenfeld ()
Additional contact information
Wen Liu: Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Bogdan Tanasa: Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Oksana V. Tyurina: Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Tian Yuan Zhou: Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Reto Gassmann: University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Wei Ting Liu: University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Kenneth A. Ohgi: Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Chris Benner: University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Ivan Garcia-Bassets: Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Aneel K. Aggarwal: Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, New York 10029, USA
Arshad Desai: University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Pieter C. Dorrestein: University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Christopher K. Glass: University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Michael G. Rosenfeld: Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA

Nature, 2010, vol. 466, issue 7305, 508-512

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/nature09272

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