Autoinhibition imposed by a large conformational switch of INO80 regulates nucleosome positioning

• 成果类型: Article
• 署名作者: Kaur, Upneet; Wu, Hao; Cheng, Yifan; Narlikar, Geeta J.
• 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: 0036-8269
• DOI: 10.1126/science.adr3831
• 发表日期: 2025-07-17
• 关键词: chromatin remodeler; core particle; recombinant histones; yeast; activation; DYNAMICS; subunit; MODEL; iswi; acf

摘要

Increasing the flanking DNA from 40 to 80 base pairs (bp) causes similar to 100-fold faster nucleosome sliding by INO80. A prevalent hypothesis posits that the Arp8 module within INO80 enables a ruler-like activity. Using cryogenic electron microscopy, we show that on nucleosomes with 40 bp of flanking DNA, the Arp8 module rotates 180 degrees away from the DNA. Deleting the Arp8 module enables rapid sliding irrespective of flanking DNA length. Thus, rather than enabling a ruler-like activity, the Arp8 module acts as a brake on INO80 remodeling when flanking DNA is short. This autoinhibition-based mechanism has broad implications for understanding how primitive nucleosome mobilization enzymes may have evolved into sophisticated remodelers.