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Cell Rep. 2017 Nov 21;21(8):2160-2170. doi: 10.1016/j.celrep.2017.10.091.

Kdm2b Regulates Somatic Reprogramming through Variant PRC1 Complex-Dependent Function.

Author information

1
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
2
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Guangzhou Branch of the Supercomputing Center of Chinese Academy of Sciences, Guangzhou 510530, China.
3
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
4
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Guangzhou Medical University, Guangzhou, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
5
State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
6
Department of Biology, Southern University of Science and Technology of China, Shenzhen 518055, China.
7
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: pei_duanqing@gibh.ac.cn.
8
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangzhou Branch of the Supercomputing Center of Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: chen_jiekai@gibh.ac.cn.

Abstract

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.

KEYWORDS:

BMP signaling; Kdm2b; PRC1; Polycomb repressive complex 1; epigenetic regulation; iPS; pluripotency; reprogramming; variant PRC1

PMID:
29166607
DOI:
10.1016/j.celrep.2017.10.091
[Indexed for MEDLINE]
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