@article{dc2b4f12a48943f9abb14198eee545b5,
title = "PRC2 Acts as a Critical Timer That Drives Oligodendrocyte Fate over Astrocyte Identity by Repressing the Notch Pathway",
abstract = "PRC2 creates the repressive mark histone H3 Lys27 trimethylation. Although PRC2 is involved in various biological processes, its role in glial development remains ambiguous. Here, we show that PRC2 is required for oligodendrocyte (OL) differentiation and myelination, but not for OL precursor formation. PRC2-deficient OL lineage cells differentiate into OL precursors, but they fail to trigger the molecular program for myelination, highlighting that PRC2 is essential for directing the differentiation timing of OL precursors. PRC2 null OL lineage cells aberrantly induce Notch pathway genes and acquire astrocytic features. The repression of the Notch pathway restores the myelination program and inhibits abnormal astrocytic differentiation in the PRC2-deficient OL lineage, indicating that Notch is a major target of PRC2. Altogether, our studies propose a specific action of PRC2 as a novel gatekeeper that determines the glial fate choice and the timing of OL lineage progression and myelination by impinging on the Notch pathway.",
keywords = "EED, Ezh2, H3K27me3, NFIA, Notch pathway, PRC2, Wnt pathway, astrocyte, myelination, oligodendrocyte",
author = "Wenxian Wang and Hyeyoung Cho and Dongkyeong Kim and Younjung Park and Moon, {Ji Hwan} and Lim, {Su Jeong} and Yoon, {Sung Min} and Michael McCane and Aicher, {Sue A.} and Sangsoo Kim and Ben Emery and Lee, {Jae W.} and Seunghee Lee and Yungki Park and Lee, {Soo Kyung}",
note = "Funding Information: We are grateful to Jo Hill for help with electron micrograph analysis, Stuart Orkin for Ezh2-flox mice, Ben Novitch and Thomas Jessell for Olig2-Cre mice, Q. Richard Lu for Olig1-Cre mice, Ben Deneen for NFIA expression vector and antibodies, Patrizia Casaccia for sharing H3K27me3 ChIP-seq dataset, Richard Goodman and Anthony P. Barnes for critically reading this manuscript, and the Lee laboratory members for helpful discussions. This research was supported by grants from NIH/NINDS ( R01NS054941 , R56NS054941 , and R01NS100471 to S.-K.L.; P30NS061800 to S.A.A.; and R01NS094181 and R21NS102558 to Yungki Park), NIH/NIDDK ( R01DK064678 and R01DK103661 to J.W.L.), and the National Multiple Sclerosis Society ( RG 5106A1 ); a Race to Erase MS grant (to B.E.), the Soongsil University Research Fund of 2018 (to S.K.), grants of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea ( HI17C0447 ) and the Medical Research Center (MRC) ( NRF-2018R1A5A2024425 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (to S.L.). Funding Information: We are grateful to Jo Hill for help with electron micrograph analysis, Stuart Orkin for Ezh2-flox mice, Ben Novitch and Thomas Jessell for Olig2-Cre mice, Q. Richard Lu for Olig1-Cre mice, Ben Deneen for NFIA expression vector and antibodies, Patrizia Casaccia for sharing H3K27me3 ChIP-seq dataset, Richard Goodman and Anthony P. Barnes for critically reading this manuscript, and the Lee laboratory members for helpful discussions. This research was supported by grants from NIH/NINDS (R01NS054941, R56NS054941, and R01NS100471 to S.-K.L.; P30NS061800 to S.A.A.; and R01NS094181 and R21NS102558 to Yungki Park), NIH/NIDDK (R01DK064678 and R01DK103661 to J.W.L.), and the National Multiple Sclerosis Society (RG 5106A1); a Race to Erase MS grant (to B.E.), the Soongsil University Research Fund of 2018 (to S.K.), grants of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0447) and the Medical Research Center (MRC) (NRF-2018R1A5A2024425) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (to S.L.). Conceptualization, W.W. and S.-K.L.; Methodology, W.W. D.K. Younjung P. S.A.A. B.E. S.L. Yungki P. and S.-K.L.; Investigation, W.W. and S.-K.L.; Formal Analysis, W.W. H.C. J.H.M. S.J.L. S.M.Y. and S.K.; Writing ? Original Draft, W.W. and S.-K.L.; Writing ? Review & Editing, W.W. J.W.L. and S.-K.L.; Supervision, J.W.L. and S.-K.L.; Funding Acquisition, S.A.A. S.K. B.E. S.L. Yungki P. J.W.L. and S.-K.L. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = sep,
day = "15",
doi = "10.1016/j.celrep.2020.108147",
language = "English (US)",
volume = "32",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}