DNA supercoiling-transcription interplay in the presence of nucleosomes*

During transcription elongation, RNA polymerases (RNAPs) positively supercoil (overtwist) the downstream DNA and negatively supercoil (untwist) the upstream DNA. The resulting torsional stress can slow down transcription elongation. In eukaryotes, steric hindrance by nucleosomes can present an additional barrier to RNAP translocation. The overall effect of how nucleosomes alter the DNA torsional response and the steric hindrance they present will dictate transcription dynamics in eukaryotes. Here, we calculate the DNA torsional response as a function of the nucleosome density and show that since nucleosomes store negative supercoiling in the relaxed configuration, they can act as buffers to lower the torsional stress from RNAP-generated DNA supercoiling. Consequently, the presence of nucleosomes can speed up transcription elongation, despite the steric hindrance. Just like prokaryotes, eukaryotic transcription is further sped-up at high RNAP recruitment rates via cooperation between co-transcribing RNAPs. RNAP-generated supercoiling also drives transcriptional bursting, and the supercoiling dynamics can dictate transcriptional noise. Overall, we present a mechanistic description of the supercoiling-transcription interplay in eukaryotes.