Klf2 is required for endoderm differentiation in mouse embryonic stem cells

Abstract

Polycomb repressive complex 1 (PRC1) plays important roles in expression of development-related genes, but precisely how PRC1 can be recruited to specific genomic loci remains unclear. Here, we show that DNA-binding transcription factor Krűppel-like factor 2 (Klf2) directly binds to Ring1b, a PRC1 subunit that has histone H2A ubiquitylation activity, and is responsible for recruitment of PRC1 to the promoter regions of several endoderm specific genes in mouse embryonic stem cells (mESCs). Klf2-deficient mESCs fail to downregulate expression of endoderm specific genes. Consistently, RNA-seq and cell differentiation analyses reveal that loss of Klf2 and Ring1b increases expression of the endoderm specific genes and facilitates endoderm differentiation. Collectively, our results suggest that Klf2 recruits PRC1 complex to the target genes and that they play roles in regulation of lineage specification and maintenance of ESC identity.