Chd2 knockout effect on chromatin remodelling and the expression of developmental genes in mouse embryonic stem cells (ChIP-Seq). Mus musculus

We demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) is required to maintain the differentiation potential of mouse ESCs. Chd2-depleted ESCs showed suppressed expression of developmentally regulated genes upon differentiation and subsequent differentiation defects without affecting gene expression in the undifferentiated state. Furthermore, chromatin immunoprecipitation followed by sequencing revealed alterations in a proportion of nucleosomes of developmentally regulated genes in Chd2-depleted ESCs to enhance histone variant H3.3 enrichment, leading to elevated trimethylation of histone H3 lysine 27.Chd2 is essential to prevent suppressive chromatin formation in developmentally regulated genes and determines subsequent effects on developmental processes in the undifferentiated state. Overall design: Evaluation of three histone modifications, H3.3 and total H3 in WT and Chd2mut/mut mESCs (ChIP-Seq), and of mRNA expression (RNA-Seq).