Abstract
Chromatin remodelers regulate the nucleosome barrier during transcription, DNA replication, and DNA repair. The chromatin remodeler RSF1 is enriched at mitotic centromeres, but the functional consequences of this enrichment are not completely understood. Shugoshin (Sgo1) protects centromeric cohesion during mitosis and requires BuB1-dependent histone H2A phosphorylation (H2A-pT120) for localization. Loss of Sgo1 at centromeres causes chromosome missegregation. Here, we show that RSF1 regulates Sgo1 localization to centromeres through coordinating a crosstalk between histone acetylation and phosphorylation. RSF1 interacts with and recruits HDAC1 to centromeres, where it counteracts TIP60-mediated acetylation of H2A at K118. This deacetylation is required for the accumulation of H2A-pT120 and Sgo1 deposition, as H2A-K118 acetylation suppresses H2A-T120 phosphorylation by Bub1. Centromeric tethering of HDAC1 prevents premature chromatid separation in RSF1 knockout cells. Our results indicate that RSF1 regulates the dynamics of H2A histone modifications at mitotic centromeres and contributes to the maintenance of chromosome stability.
Highlights
Chromatin remodelers regulate the nucleosome barrier during transcription, DNA replication, and DNA repair
We show that premature chromosome segregation in RSF1 knockout (KO) cells is triggered by defects in Sgo[1] binding to centromeres
We further show that RSF1 recruits HDAC1 to centromeres, and HDAC1-mediated deacetylation of H2A at K118 is a prerequisite for the accumulation of H2ApT120 and Sgo[1] deposition
Summary
Chromatin remodelers regulate the nucleosome barrier during transcription, DNA replication, and DNA repair. Shugoshin (Sgo1) protects centromeric cohesion during mitosis and requires BuB1-dependent histone H2A phosphorylation (H2A-pT120) for localization. We show that RSF1 regulates Sgo[1] localization to centromeres through coordinating a crosstalk between histone acetylation and phosphorylation. RSF1 interacts with and recruits HDAC1 to centromeres, where it counteracts TIP60-mediated acetylation of H2A at K118 This deacetylation is required for the accumulation of H2A-pT120 and Sgo[1] deposition, as H2A-K118 acetylation suppresses H2A-T120 phosphorylation by Bub[1]. We have recently shown that RSF1 localizes to mitotic centromeres and recruits PLK1 for stable kinetochore-microtubule attachment[11]. Sororin and cohesion are protected from phosphorylation by the shugoshin[1] (Sgo1) and protein phosphatase 2A (PP2A) complex[24,25]. We propose that RSF1 coordinates a crosstalk between histone acetylation and phosphorylation and tunes histone marks at centromeres to maintain chromosome stability
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
