RNF20 and USP44 Regulate Stem Cell Differentiation by Modulating H2B Monoubiquitylation

Gilad Fuchs, Efrat Shema, Rita Vesterman, Eran Kotler, Zohar Wolchinsky, Sylvia Wilder, Lior Golomb, Ariel Pribluda, Feng Zhang, Mahmood Haj-Yahya, Ester Feldmesser, Ashraf Brik, Xiaochun Yu, Jacob Hanna, Daniel Aberdam, Eytan Domany, Moshe Oren

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

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.

Original languageEnglish
Pages (from-to)662-673
Number of pages12
JournalMolecular Cell
Volume46
Issue number5
DOIs
StatePublished - 8 Jun 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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