@article{ca5eafb588494212b91d3a915530e22e,
title = "CpG island reconfiguration for the establishment and synchronization of polycomb functions upon exit from naive pluripotency",
abstract = "Polycomb group (PcG) proteins are essential for post-implantation development by depositing repressive histone modifications at promoters, mainly CpG islands (CGIs), of developmental regulator genes. However, promoter PcG marks are erased after fertilization and de novo established in peri-implantation embryos, coinciding with the transition from naive to primed pluripotency. Nevertheless, the molecular basis for this establishment remains unknown. In this study, we show that the expression of the long KDM2B isoform (KDM2BLF), which contains the demethylase domain, is specifically induced at peri-implantation and that its H3K36me2 demethylase activity is required for PcG enrichment at CGIs. Moreover, KDM2BLF interacts with BRG1/BRM-associated factor (BAF) and stabilizes BAF occupancy at CGIs for subsequent gain of accessibility, which precedes PcG enrichment. Consistently, KDM2BLF inactivation results in significantly delayed post-implantation development. In summary, our data unveil dynamic chromatin configuration of CGIs during exit from naive pluripotency and provide a conceptual framework for the spatiotemporal establishment of PcG functions.",
keywords = "BRG1, CpG islands, H2AK119ub, H3K27me3, H3K36me2, SWI/SNF, accessibility, demethylation, polycomb, post-implantation development",
author = "Dawei Huo and Zhaowei Yu and Rui Li and Meihan Gong and Simone Sidoli and Xukun Lu and Yuying Hou and Zhongye Dai and Yu Kong and Guifen Liu and Jensen, {Ole N.} and Wei Xie and Kristian Helin and Chaoyang Xiong and Guohong Li and Yong Zhang and Xudong Wu",
note = "Funding Information: We thank members of the Wu and Helin labs for insightful comments and discussions over the course of the study. We are grateful to Deqing Hu (TMU) for providing critical comments on the manuscript and for helpful discussions. This study was supported by the National Key Research and Development Program ( 2017YFA0504102 to X.W.), the National Natural Science Foundation of China ( 81772676 and 31970579 to X.W.; 32001025 to D.H.; 32030022 to Y.Z.), the Natural Science Foundation of Tianjin Municipal Science and Technology Commission ( 18JCJQJC48200 to X.W.), Key Research Project of Tianjin Education Commission ( 2020ZD13 to X.W.), an open grant from Chinese Academy of Medical Sciences ( 157-Z20-04 to X.W.), and the National Youth Talent Support Program to X.W. The work was also supported by an HHMI International Research Scholar grant ( 55008737 ) to G.L. and the Danish National Research Foundation ( DNRF82 ) to K.H. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = mar,
day = "17",
doi = "10.1016/j.molcel.2022.01.027",
language = "English (US)",
volume = "82",
pages = "1169--1185.e7",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}