Chromatin buffers torsional stress during transcription.

Abstract

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.