The chromatin remodeler RSF1 controls centromeric histone modifications to coordinate chromosome segregation

Ho-Soo Lee, Zhonghui Lin, Sunyoung Chae, Young-Suk Yoo, Byung-Gyu Kim, Youngsoo Lee, Jared L. Johnson, You-Sun Kim, Lewis C. Cantley, Chang-Woo Lee, Hongtao Yu () and Hyeseong Cho ()
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Ho-Soo Lee: Ajou University School of Medicine
Zhonghui Lin: University of Texas Southwestern Medical Center
Sunyoung Chae: Institute of Medical Science, Ajou University School of Medicine
Young-Suk Yoo: Ajou University School of Medicine
Byung-Gyu Kim: Center for Genomic Integrity, Institute for Basic Science, UNIST
Youngsoo Lee: Genomic Instability Research Center, Ajou University School of Medicine
Jared L. Johnson: Weill Cornell Medical College
You-Sun Kim: Ajou University School of Medicine
Lewis C. Cantley: Weill Cornell Medical College
Chang-Woo Lee: Sungkyunkwan University School of Medicine
Hongtao Yu: University of Texas Southwestern Medical Center
Hyeseong Cho: Ajou University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06377-w

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