FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics

Melesse Nune, Michael Morgan, Zaily Connell, Laura McCullough, Muhammad Jbara, Hao Sun, Ashraf Brik, Tim Formosa, Cynthia Wolberger

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Jan 25 2019

Fingerprint

Nucleosomes
Transcription
DNA Replication
Yeast
Histone Chaperones
Yeasts
Hydroxyurea
DNA
Substrates
Histones
Genes
Phenotype

Keywords

  • biochemistry
  • chemical biology
  • chromosomes
  • deubiquitinating enzyme
  • DNA replication
  • gene expression
  • histone chaperone
  • nucleosome dynamics
  • S. cerevisiae
  • transcription
  • ubiquitin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics. / Nune, Melesse; Morgan, Michael; Connell, Zaily; McCullough, Laura; Jbara, Muhammad; Sun, Hao; Brik, Ashraf; Formosa, Tim; Wolberger, Cynthia.

In: eLife, Vol. 8, 25.01.2019.

Research output: Contribution to journalArticle

Nune, Melesse ; Morgan, Michael ; Connell, Zaily ; McCullough, Laura ; Jbara, Muhammad ; Sun, Hao ; Brik, Ashraf ; Formosa, Tim ; Wolberger, Cynthia. / FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics. In: eLife. 2019 ; Vol. 8.
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AU - Sun, Hao

AU - Brik, Ashraf

AU - Formosa, Tim

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