Bromodomains regulate dynamic targeting of the PBAF chromatin-remodeling complex to chromatin hubs

Charles A. Kenworthy, Nayem Haque, Shu Hao Liou, Panagiotis Chandris, Vincent Wong, Patrycja Dziuba, Luke D. Lavis, Wei Li Liu, Robert H. Singer, Robert A. Coleman

Research output: Contribution to journalArticlepeer-review

Abstract

Chromatin remodelers actively target arrays of acetylated nucleosomes at select enhancers and promoters to facilitate or shut down the repeated recruitment of RNA polymerase II during transcriptional bursting. It is poorly understood how chromatin remodelers such as PBAF dynamically target different chromatin states inside a live cell. Our live-cell single-molecule fluorescence microscopy study reveals chromatin hubs throughout the nucleus where PBAF rapidly cycles on and off the genome. Deletion of PBAF's bromodomains impairs targeting and stable engagement of chromatin in hubs. Dual color imaging reveals that PBAF targets both euchromatic and heterochromatic hubs with distinct genome-binding kinetic profiles that mimic chromatin stability. Removal of PBAF's bromodomains stabilizes H3.3 binding within chromatin, indicating that bromodomains may play a direct role in remodeling of the nucleosome. Our data suggests that PBAF's dynamic bromodomain-mediated engagement of a nucleosome may reflect the chromatin-remodeling potential of differentially bound chromatin states.

Original languageEnglish (US)
Pages (from-to)1738-1752
Number of pages15
JournalBiophysical journal
Volume121
Issue number9
DOIs
StatePublished - May 3 2022

Keywords

  • bromodomain
  • chromatin remodeling
  • histone acetylation
  • histone H3.3
  • nuclear hubs
  • PBAF
  • single-molecule tracking

ASJC Scopus subject areas

  • Biophysics

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