Kdm2b Regulates Somatic Reprogramming through Variant PRC1 Complex-Dependent Function

作者：Zhou, Zhiwei; Yang, Xuejie; He, Jiangping; Liu, Jing; Wu, Fang; Yu, Shengyong; Liu, Yuting; Lin, Runxia; Liu, He; Cui, Yuanbin; Zhou, Chunhua; Wang, Xiaoshan; Wu, Jian; Cao, Shangtao; Guo, Lin; Lin, Lihui; Wang, Tao; Peng, Xiaozhong; Qiang, Boqing; Hutchins, Andrew P.; Pei, Duanqing; Chen, Jiekai

来源：Cell Reports, 2017, 21(8): 2160-2170.

DOI：10.1016/j.celrep.2017.10.091

• H2A UBIQUITYLATION
• CPG ISLANDS
• HISTONE H3
• POLYCOMB
• FAMILY
• PROTEINS
• RYBP
• DEMETHYLATION
• RECRUITMENT
• GENES

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 complex; however, little is known about the functional consequences of these variant PRC1 complexes on cell-fate determination. Here, we show that Kdm2b promotes Oct4-induced somatic reprogramming through recruitment of a variant PRC1 complex (PRC1.1) to CpG islands (CGIs). Furthermore, we find that bone morphogenetic protein (BMP) represses Oct4/Kdm2b-induced somatic reprogramming selectively. Mechanistically, BMP-SMAD pathway attenuates PRC1.1 occupation and H2AK119 ubiquitination at genes linked to development, resulting in the expression of mesendodermal factors such as Sox17 and a consequent suppression of somatic reprogramming. These observations reveal that PRC1.1 participates in the establishment of pluripotency and identify BMP4 signaling as a modulator of PRC1.1 function.

• 出版日期2017-11-21
• 单位医学分子生物学国家重点实验室; 华南理工大学; 中国医学科学院北京协和医院; 广州医科大学; 中国科学技术大学; 中国科学院; 北京协和医学院; 中国科学院大学; 中国科学院广州生物医药与健康研究院