Structural basis of transcription-coupled H3K36 trimethylation by Set2 and RNAPII elongation complex in the nucleosome

Kujirai, T.; Ehara, H.; Ito, T.; Henmi, M.; Sekine, S.-i.; Kurumizaka, H.

doi:10.1101/2024.12.13.628464

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bioRxiv · 10.1101/2024.12.13.628464

Structural basis of transcription-coupled H3K36 trimethylation by Set2 and RNAPII elongation complex in the nucleosome

Kujirai, T.·Ehara, H.·Ito, T.·Henmi, M.·Sekine, S.-i.·Kurumizaka, H.

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Abstract

Trimethylation of the histone H3K36 residue (H3K36me3) plays an indispensable role in ensuring transcription fidelity by suppressing undesired cryptic transcription in chromatin. The H3K36me3 modification is accomplished by Set2/SETD2 during transcription elongation by the RNA polymerase II elongation complex (EC). Here we found that the Set2-mediated H3K36me3 deposition occurs primarily on the nucleosome reassembling behind the EC. Cryo-electron microscopy structures of the transcribing EC complexed with Set2 and the reassembled nucleosome revealed that Set2 is anchored by the Spt6 subunit of the EC and captures an H3 N-terminal tail of the nucleosome. Abrogation of the Set2-Spt6 interaction leads to defective transcription-coupled H3K36me3 deposition. These insights elucidate the structure-based mechanism of transcription-coupled H3K36me3 deposition in chromatin. One-Sentence SummaryCryo-EM structures of the EC-Set2-nucleosome complex reveal the mechanism of H3 Lys36 trimethylation in chromatin.

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Kujirai, T., Ehara, H., Ito, T., Henmi, M., Sekine, S.-i., Kurumizaka, H.. 2024-12-14. Structural basis of transcription-coupled H3K36 trimethylation by Set2 and RNAPII elongation complex in the nucleosome. https://doi.org/10.1101/2024.12.13.628464

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