Reorientation of INO80 on hexasomes reveals basis for mechanistic versatility

• 成果类型: Article
• 署名作者: Wu, Hao; Munoz, Elise N.; Hsieh, Laura J.; Chio, Un Seng; Gourdet, Muryam A.; Narlikar, Geeta J.; Cheng, Yifan
• 署名单位: University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13707
• DOI: 10.1126/science.adf4197
• 发表日期: 2023-07-21
• 页码: 319-324
• 关键词: nucleosome core particle; recombinant histones; chromatin dynamics; dna translocation; transcription; remodeler

摘要

Unlike other chromatin remodelers, INO80 preferentially mobilizes hexasomes, which can form during transcription. Why INO80 prefers hexasomes over nucleosomes remains unclear. Here, we report structures of Saccharomyces cerevisiae INO80 bound to a hexasome or a nucleosome. INO80 binds the two substrates in substantially different orientations. On a hexasome, INO80 places its ATPase subunit, Ino80, at superhelical location -2 (SHL -2), in contrast to SHL -6 and SHL -7, as previously seen on nucleosomes. Our results suggest that INO80 action on hexasomes resembles action by other remodelers on nucleosomes such that Ino80 is maximally active near SHL -2. The SHL -2 position also plays a critical role for nucleosome remodeling by INO80. Overall, the mechanistic adaptations used by INO80 for preferential hexasome sliding imply that subnucleosomal particles play considerable regulatory roles.