Replication‐independent chromatin loading of Dnmt1 during G2 and M phases

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<jats:p>The major DNA methyltransferase, Dnmt1, associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand. In view of the slow kinetics of Dnmt1 <jats:italic>in vitro</jats:italic> versus the fast progression of the replication fork, we have tested whether Dnmt1 associates with chromatin beyond S phase. Using time‐lapse microscopy of mammalian cells expressing green‐fluorescent‐protein‐tagged Dnmt1 and DsRed‐tagged DNA Ligase I as a cell cycle progression marker, we have found that Dnmt1 associates with chromatin during G2 and M. This association is mediated by a specific targeting sequence, shows strong preference for constitutive but not facultative heterochromatin and is independent of heterochromatin‐specific histone H3 Lys 9 trimethylation, SUV39H and HP1. Moreover, photobleaching analyses showed that Dnmt1 is continuously loaded onto chromatin throughout G2 and M, indicating a replication‐independent role of Dnmt1 that could represent a novel and separate pathway to maintain DNA methylation.</jats:p>

収録刊行物

  • EMBO reports

    EMBO reports 5 (12), 1181-1186, 2004-12

    Springer Science and Business Media LLC

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