UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells

TLDR

Epigenetic inheritance in mammals relies on robust propagation of DNA methylation patterns throughout development. UHRF1 contains an SRA domain that preferentially binds hemimethylated CG sites, the physiological substrate for DNMT1. UHRF1 is required for maintaining DNA methylation, colocalizes with DNMT1 during S phase, interacts directly with DNMT1 to tether it to chromatin, and likely recruits DNMT1 to hemimethylated DNA to facilitate faithful maintenance of methylation.

Abstract

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.