YTHDF1 facilitates PRC1 mediated H2AK119ub in Human ES Cells

Polycomb repressive complexes( PRCs) play critical role in cell fate decisions during normal development as well as disease progression through mediate histone modifications such as H3K27me3 and H2AK119ub. How exactly PRCs recruited to chromatin remains to be fully illuminated. Here, we report that YTHDF1, a N6-methyladenine (m6A) RNA reader previously known being mainly cytoplasmic, associates with RNF2, a PRC1 protein that mediates H2AK119ub in human embryonic stem cells (hESCs). Specifically, a portion of YTHDF1 localizes in the nuclei and associates with RNF2/ H2AK119ub on a subset of gene loci related to neural development functions. Knock-down YTHDF1 attenuates H2AK119ub modification on these genes and promotes neural differentiation in hESCs. Our findings provide another non-canonical mechanism of YTHDF1 to participate in PRC1 mediated chromatin modification in hESCs. Overall design: We compared the YTHDF1, RNF2 binding sites and H2AK119ub modified sites in WT human ESCs by CHIP-seq. Meanwhile we also compared YTHDF1 signal in YTHDF1 KD and WT human ESCs by ChIP-seq. ChIP-seq experiments were performed in two biological replicates, and ChIP-seq Replicates were merged into one BED file.