RNF20 and USP44 Regulate Stem Cell Differentiation by Modulating H2B Monoubiquitylation

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, monoubi...

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Bibliographic Details
Published in:Molecular cell 2012-06, Vol.46 (5), p.662-673
Main Authors: Fuchs, Gilad, Shema, Efrat, Vesterman, Rita, Kotler, Eran, Wolchinsky, Zohar, Wilder, Sylvia, Golomb, Lior, Pribluda, Ariel, Zhang, Feng, Haj-Yahya, Mahmood, Feldmesser, Ester, Brik, Ashraf, Yu, Xiaochun, Hanna, Jacob, Aberdam, Daniel, Domany, Eytan, Oren, Moshe
Format: Article
Language:English
Subjects:
Animals
cell differentiation
Cell Differentiation - genetics
chromatin
Chromatin Assembly and Disassembly
Down-Regulation
embryonic stem cells
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Endopeptidases - metabolism
Endopeptidases - physiology
Epigenesis, Genetic
genes
histones
Histones - metabolism
Humans
lysine
Mice
Models, Genetic
plasticity
transcription (genetics)
ubiquitin-protein ligase
Ubiquitin-Protein Ligases - metabolism
Ubiquitin-Protein Ligases - physiology
Ubiquitin-Specific Proteases
Ubiquitination
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Summary: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. ► Differentiation is associated with an increase in histone H2B monoubiquitylation ► RNF20 is necessary for optimal differentiation ► RNF20 is required for induction of long genes during differentiation ► USP44 negatively regulates H2B ubiquitylation
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2012.05.023