Lsh Is Essential for Maintaining Global DNA Methylation Levels in Amphibia and Fish and Interacts Directly with Dnmt1

Figure 4

Model for Lsh and Dnmt1 cooperation in silencing. (a) Model for Lsh:Dnmt1 mediated repression. In wild type cells, the H3K9trime mark acts as a ligand in HP1α recruitment to silent regions of the genome. Taking together our data and that of others, both Dnmt1 and Lsh can be associated with HP1α (perhaps requiring HDACs 1 and 2) thereby allowing the parallel docking of DNA methyltransferase and chromatin remodelling activities to silent loci. (b) In Lsh depleted cells (and knockout plants and animals), targeting of Dnmt1 is diminished leading to reduced DNA methylation maintenance and partial genomic hypomethylation. The accumulation of the activating H3K4me2 mark in cells may be a downstream effect of DNA hypomethylation.

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