FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics
- Johns Hopkins University School of Medicine, United States
- University of Utah School of Medicine, United States
- Technion-Israel Institute of Technology, Israel
Abstract
Monoubiquitination of histone H2B (H2B-Ub) plays a role in transcription and DNA replication, and is required for normal localization of the histone chaperone, FACT. In yeast, H2B-Ub is deubiquitinated by Ubp8, a subunit of SAGA, and Ubp10. Although they target the same substrate, loss of Ubp8 and Ubp10 cause different phenotypes and alter the transcription of different genes. We show that Ubp10 has poor activity on yeast nucleosomes, but that the addition of FACT stimulates Ubp10 activity on nucleosomes and not on other substrates. Consistent with a role for FACT in deubiquitinating H2B in vivo, a FACT mutant strain shows elevated levels of H2B-Ub. Combination of FACT mutants with deletion of Ubp10, but not Ubp8, confers increased sensitivity to hydroxyurea and activates a cryptic transcription reporter, suggesting that FACT and Ubp10 may coordinate nucleosome assembly during DNA replication and transcription. Our findings reveal unexpected interplay between H2B deubiquitination and nucleosome dynamics.
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All data generated or analyzed during this study are included in the manuscript and supporting files.
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Author details
Funding
National Institute of General Medical Sciences (GM095822)
- Cynthia Wolberger
National Institute of General Medical Sciences (GM064649)
- Tim Formosa
National Science Foundation (Graduate Research Fellowship)
- Melesse Nune
Jordan and Irene Tark Academic Chair
- Ashraf Brik
Israel Council of Higher Education (Fellowship)
- Muhammad Jbara
National Institute of General Medical Sciences (Training Grant GM008403)
- Melesse Nune
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Nune et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics
eLife 8:e40988.
https://doi.org/10.7554/eLife.40988
