Kdm2b regulates somatic reprogramming through variant PRC1 complex dependent function [ChIP-seq, MeDIP-seq]

Polycomb repressive complex 1 (PRC1) plays essential roles in cell fate determination. Recent studies have found that the composition of mammalian PRC1 is particularly varied and complicated, whereas the function of such variant PRC1 complexes on cell fate determination remains unknown. Here we show that Kdm2b, which recruits a variant PRC1 complex (PRC1.1) to CpG islands (CGIs), elevates Oct4 induced somatic reprogramming. Interaction with PRC1 is critical for Kdm2b's promotion on the process of induced pluripotency. Furthermore, we find that bone morphogenetic proteins (BMPs) repress Oct4/Kdm2b induced somatic reprogramming selectively. Mechanistically, BMP-Smad pathway attenuates PRC1.1 occupation and H2AK119 ubiquitination on development genes, resulting in the release of meso-endoderm factors such as Sox17 and suppression of somatic reprogramming. These observations reveal that PRC1.1 participates in the establishment of pluripotency as well as cellular differentiation and identify BMP signal as a modulator of PRC1.1 function. Overall design: We analyzed the gene expression profiles and PRC1.1 occupation on chromatin during the Oct4/Kdm2b induced reprogramming process by RNA-seq and ChIP-seq. We performed ChIP-seq of KDM2B,H2AK119ub, H3K36me2, H3K27me3 and 5mC-MeDIP-seq in Oct4/DR(ODR), Oct4/Kdm2a(OA), Oct4/Kdm2b(OB) mediated reprogramming cells at day14. We also performed ChIP-seq of KDM2B,H2AK119ub and RING1B in Oct4/Kdm2b/Id1(OBD) mediated reprogramming cells at day9.