Chromatin buffers torsional stress during transcription
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·nm) alone and 13 pN·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.
Authors
- Glenn Hauk (ORCID: https://orcid.org/0000-0003-4325-7335)
- Joshua Jeong (ORCID: https://orcid.org/0000-0002-5417-8467)
- Michelle D. Wang (ORCID: https://orcid.org/0000-0001-9137-3790)
- Lucyna Lubkowska
- James T. Inman (ORCID: https://orcid.org/0000-0003-3534-0323)
- Deanna Gotte (ORCID: https://orcid.org/0009-0006-6581-8171)
- Xiaomeng Jia (ORCID: https://orcid.org/0000-0002-1754-7198)
- James M. Berger (ORCID: https://orcid.org/0000-0003-0666-1240)
- Robert M. Fulbright (ORCID: https://orcid.org/0009-0004-6323-6472)
- Mikhail Kashlev (ORCID: https://orcid.org/0000-0002-1260-6486)
- Yifeng Hong (ORCID: https://orcid.org/0000-0002-4444-4848)
- Shuming Zhang (ORCID: https://orcid.org/0000-0002-2424-1824)
- Chuang 创 Tan 谭 (ORCID: https://orcid.org/0009-0008-8298-9014)
- Jin Qian (ORCID: https://orcid.org/0009-0001-0034-0246)
- Teresa Kay (ORCID: https://orcid.org/0000-0003-3622-2281)
Institutions
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- Cornell University (US)
- Johns Hopkins Medicine (US)
- National Cancer Institute (US)
- Center for Cancer Research (US)
Publication Details
- Journal
- Science
- Published
- 2025-12-18
- DOI
- https://doi.org/10.1126/science.adv0134
- Citations
- 1
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.81