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Originally published in Science Express on 2 August 2007
Science 21 September 2007:
Vol. 317. no. 5845, pp. 1760 - 1764
DOI: 10.1126/science.1147939
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Reports

UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells

Magnolia Bostick,1* Jong Kyong Kim,2* Pierre-Olivier Estève,2 Amander Clark,1 Sriharsa Pradhan,2{dagger} Steven E. Jacobsen1,3{dagger}

Epigenetic inheritance in mammals relies in part on robust propagation of DNA methylation patterns throughout development. We show that the protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1), also known as NP95 in mouse and ICBP90 in human, is required for maintaining DNA methylation. UHRF1 colocalizes with the maintenance DNA methyltransferase protein DNMT1 throughout S phase. UHRF1 appears to tether DNMT1 to chromatin through its direct interaction with DNMT1. Furthermore UHRF1 contains a methyl DNA binding domain, the SRA (SET and RING associated) domain, that shows strong preferential binding to hemimethylated CG sites, the physiological substrate for DNMT1. These data suggest that UHRF1 may help recruit DNMT1 to hemimethylated DNA to facilitate faithful maintenance of DNA methylation.

1 Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
2 New England BioLabs, Ipswich, MA 01938, USA.
3 Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: pradhan{at}neb.com (S.P.); jacobsen{at}ucla.edu (S.E.J.)

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