Coordinated repression of ZGA genes by methyltransferase EHMT2 via LINE1 regulatory elements

ABSTRACT: Mouse embryonic stem cells (mESCs) can reverse typical developmental trajectories and de-differentiate into 2-cell-like cells (2CLCs) that resemble the mammalian embryo during zygotic genome activation (ZGA). We have dissected molecular functions of the chromatin repressor EHMT2, a candidate antagonist of the mESC-to-2CLC transition, by leveraging a multipurpose allele for acute protein depletion and efficient immunoprecipitation. We show here that EHMT2 directly represses large clusters of co-regulated gene loci, which comprise a significant fraction of the 2CLC-specific transcriptome, by initiating H3K9me2 spreading from distal LINE-1 elements. Thereby, EHMT2 counteracts the recruitment of the activator DPPA2/4 to promoter-proximal endogenous retroviral elements (ERVs) at 2CLC genes. EHM

SUBMITTER: Matthias Stadtfeld 

PROVIDER: S-SCDT-10_1038-S44319-025-00657-5 | biostudies-other |

REPOSITORIES: biostudies-other