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Fragile nucleosomes are essential for RNA Polymerase II to transcribe in eukaryotes

Li, L.; Hunter, S.; Leach, S.; Zhuang, Y.; Liu, H.; Gao, J.; Zhang, Q.; Stasevich, T. J.; Kimura, H.; Dowell, R. D.; Zhang, G.

2025-10-11 genetics
10.1101/2025.10.08.681188 bioRxiv
Show abstract

Nucleosomes are barriers to RNA Polymerase II (Pol II) transcribing along gene bodies in eukaryotes. We found that a fragile "tailless nucleosome" could be generated to resolve the Pol II pausing caused by the +1 nucleosome in metazoans. We hypothesized that "pan-acetylated nucleosomes" along gene bodies are fragile and are generated to resolve the resistance of nucleosomes to the elongation of Pol II. To confirm this hypothesis, we systematically analyzed pan-acetylation and pan-phosphorylation of the entire human genome in HEK293T cells. Herein, we show that both pan-acetylation and pan-phosphorylation of histones in nucleosomes along gene bodies are coupled with the activities of Pol II. Our results show that there are four major types of fragile nucleosomes required for Pol II to transcribe along gene bodies: nucleosomes without tails, nucleosomes with dominant acetylation, nucleosomes with dominant phosphorylation, and nucleosomes with both acetylation and phosphorylation.

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