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Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation.

A fundamental challenge in mammalian biology has been the elucidation of mechanisms linking DNA methylation and histone post-translational modifications. Human UHRF1 (ubiquitin-like PHD and RING finger domain-containing 1) has multiple domains that bind chromatin, and it is implicated genetically in the maintenance of DNA methylation. However, molecular mechanisms underlying DNA methylation regulation by UHRF1 are poorly defined. Here we show that UHRF1 association with methylated histone H3 Lys9 (H3K9) is required for DNA methylation maintenance. We further show that UHRF1 association with H3K9 methylation is insensitive to adjacent H3 S10 phosphorylation--a known mitotic 'phospho-methyl switch'. Notably, we demonstrate that UHRF1 mitotic chromatin association is necessary for DNA methylation maintenance through regulation of the stability of DNA methyltransferase-1. Collectively, our results define a previously unknown link between H3K9 methylation and the faithful epigenetic inheritance of DNA methylation, establishing a notable mitotic role for UHRF1 in this process.

Pubmed ID: 23022729 RIS Download

Mesh terms: Amino Acid Sequence | CCAAT-Enhancer-Binding Proteins | Chromatin | Cloning, Molecular | DNA Methylation | DNA Primers | Epigenesis, Genetic | Escherichia coli | Fluorescence Polarization | HeLa Cells | Histones | Humans | Magnetic Resonance Spectroscopy | Microarray Analysis | Mitosis | Molecular Sequence Data | Phosphorylation

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GenBank

NIH genetic sequence database that provides an annotated collection of all publicly available DNA sequences for almost 280 000 formally described species. (Jan 2014) These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of the International Nucleotide Sequence Database Collaboration and daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP.

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