@article{9ac1ca12610742869f787c0a292e1fea,
title = "RNF20 and USP44 Regulate Stem Cell Differentiation by Modulating H2B Monoubiquitylation",
abstract = "Embryonic stem cells (ESCs) maintain high genomic plasticity, which is essential for their capacity to enter diverse differentiation pathways. Posttranscriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2Bub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of relatively long genes during ESC differentiation. Furthermore, we identify the deubiquitinase USP44 as a negative regulator of H2B ubiquitylation, whose downregulation during ESC differentiation contributes to the increase in H2Bub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner.",
author = "Gilad Fuchs and Efrat Shema and Rita Vesterman and Eran Kotler and Zohar Wolchinsky and Sylvia Wilder and Lior Golomb and Ariel Pribluda and Feng Zhang and Mahmood Haj-Yahya and Ester Feldmesser and Ashraf Brik and Xiaochun Yu and Jacob Hanna and Daniel Aberdam and Eytan Domany and Moshe Oren",
note = "Funding Information: We thank Steve Elledge and Frank Stegmeier for the USP44 plasmids; Yael Aylon, Debora-Rosa Bublik, Tingting Yao, and Robert E. Cohen for insightful discussions; Elena Ainbinder and Gilad Beck for generating shRNF20 mESCs; Gilgi Friedlander for initial microarray analysis; and Tamar Unger and Dikla Hiya for recombinant USP44. This work was supported in part by grant R37 CA40099 from the National Cancer Institute, grant 293438 (RUBICAN) from the European Research Council, the Dr. Miriam and Sheldon Adelson Medical Research Foundation, The Lower Saxony-Israeli Association (to M.O.), the Leir Charitable Foundation (to E.D.), the Edmond J. Safra Foundation (to A.B.), and the Israel Science Foundation and the French Agency for Research-Genopat08 (to D.A.). M.O. is incumbent of the Andre Lwoff chair in Molecular Biology, and E.D. is incumbent of the Henry J. Leir Professorial Chair. E.S. is supported by the Adams Fellowship Program of the Israel Academy of Sciences and Humanities. ",
year = "2012",
month = jun,
day = "8",
doi = "10.1016/j.molcel.2012.05.023",
language = "English",
volume = "46",
pages = "662--673",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",
}