PRMT7 Functionally Associates With H2AK119ub at HOX Gene Promoters as Well as HOX Gene Expression in Mouse Embryonic Stem Cells

ABSTRACT

Ubiquitination of histone H2A at lysine 119 (H2AK119ub) is a well‐established repressive chromatin mark critical for Hox gene repression in mouse embryonic stem cells (mESCs). Protein arginine methyltransferase 7 (PRMT7) has also been reported to repress HOX gene expression in embryonic carcinoma by antagonizing H3K4 methylation. However, whether PRMT7 functionally associates with H2AK119ub to reinforce HOX gene repression remains unclear. Here, we identify a positive functional relationship between PRMT7 and H2AK119ub. Genetic knockout, knockdown, or pharmacological inhibition of PRMT7 markedly reduced global H2AK119ub levels. Genome‐wide analyses revealed PRMT7 and H2AK119ub colocalize at the promoter regions of Hox genes from all four Hox clusters in mESCs. Prmt7 knockdown also decreased H2AK119ub enrichment at Hox gene promoters. Importantly, Prmt7 silencing produced a gene expression profile similar to that observed following Ring1A/1B double knockdown, including the upregulation of Hox and many other shared target genes. These findings suggest that the PRMT7–H2AK119ub axis contributes to the transcriptional repression of Hox genes in mESCs. Collectively, our study reveals a previously unrecognized functional connection between PRMT7 and H2AK119ub in the regulation of Hox gene expression.