Chromatin buffers torsional stress during transcription

• 成果类型: Article
• 署名作者: Qian, Jin; Lubkowska, Lucyna; Zhang, Shuming; Tan, Chuang; Hong, Yifeng; Jia, Xiaomeng; Fulbright, Robert M.; Inman, James T.; Kay, Taryn M.; Jeong, Joshua; Hauk, Glenn; Gotte, Deanna; Berger, James M.; Kashlev, Mikhail; Wang, Michelle D.
• 署名单位: Cornell University; Cornell University; Cornell University; Howard Hughes Medical Institute; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Cornell University; Cornell University; Johns Hopkins University; Johns Hopkins Medicine; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adv0134
• 发表日期: 2026-03-26
• 页码: eadv0134
• 关键词: rna-polymerase-ii; NUCLEOSOME CORE PARTICLE; DNA TOPOISOMERASE; structural basis; UPSTREAM DNA; elongation; replication; mechanism; initiation; conflicts

摘要

During eukaryotic transcription, RNA polymerase II (Pol II) must overcome nucleosome obstacles and, because of DNA's helical structure, must also rotate relative to DNA, which generates torsional stress. However, there is limited understanding of how Pol II transcribes through nucleosomes while supercoiling DNA. In this work, we determined that Pol II generates a torque of 9 piconewton-nanometers (pN & centerdot;nm) alone and 13 pN & centerdot;nm with transcription factor IIS (TFIIS), making it a powerful rotary motor. When Pol II encounters a nucleosome, passage becomes more efficient on a chromatin substrate compared with on a single-nucleosome substrate, which demonstrates that chromatin substantially buffers torsional stress during transcription. Furthermore, topoisomerase supercoiling relaxation allows Pol II to transcribe through multiple nucleosomes. Our results reveal a role of chromatin beyond the more conventional view of it being just a roadblock to transcription.