Article

UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science (New York, NY)

Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Science (Impact Factor: 33.61). 10/2007; 317(5845):1760-4. DOI: 10.1126/science.1147939
Source: PubMed

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.

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Available from: Pierre-Olivier Estève, Jan 13, 2014
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    • "DNA methyltransferase 1 (DNMT1) mediates inheritance of DNA methylation patterns by daughter cells from parental cells [5]. It has been reported that Np95 is required for the recruitment of DNMT1 to hemi-methylated DNA generated at the replication fork during the S-phase [6], and that Np95 binds to hemimethylated DNA through its SET and RING finger-associated (SRA) domain [7]. We have investigated the function of Stella, a maternal factor essential for early embryogenesis. "
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    • "Cell-Cycle-Dependent USP7 Regulation of UHRF1 UHRF1 has emerged as an important epigenetic regulator in the maintenance of DNA methylation through regulating the recruitment and stability of DNMT1 (Bostick et al., 2007; Du et al., 2010; Sharif et al., 2007). This regulation is achieved, in part, through dynamic regulation of UHRF1—both at the level of its chromatin association and ubiquitination—throughout the cell cycle (Gelato et al., 2014; Ma et al., 2012; Taylor et al., 2013). "
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    • "DNMT1, on the other hand, has a preference for hemi-methylated DNA. It is thought to follow the replication fork via interactions with PCNA (Chuang et al. 1997) and UHRF1 (Bostick et al. 2007; Sharif et al. 2007), in restoring DNA CpG methylation on the hemi-methylated DNA after synthesis of the daughter strand. DNA methylation is generally associated with repressed regions of the genome. "
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