2026-01-29 東京大学,理化学研究所
RNA ポリメラーゼ II による転写に伴うヒストンメチル化酵素 Set2 によるヒストンメチル化
<関連情報>
- https://www.iqb.u-tokyo.ac.jp/pressrelease/260129/
- https://www.science.org/doi/10.1126/sciadv.aed1952
FACTと協調したSet2による転写共役H3K36トリメチル化の構造的基礎 Structural basis of transcription-coupled H3K36 trimethylation by Set2 in coordination with FACT
Tomoya Kujirai, Haruhiko Ehara, Tomoko Ito, Masami Henmi, […] , and Hitoshi Kurumizaka
Science Advances Published:28 Jan 2026
DOI:https://doi.org/10.1126/sciadv.aed1952
Abstract
Trimethylation of the histone H3K36 residue (H3K36me3) plays an indispensable role in ensuring transcription fidelity by suppressing undesired cryptic transcription in chromatin. H3K36me3 modification is accomplished by Set2/SETD2 during transcription elongation by the RNA polymerase II elongation complex (EC). Here, we found that Set2-mediated H3K36me3 deposition occurs on the nucleosome reassembling behind the EC. The histone chaperone FACT suppresses H3K36me3 deposition on the downstream nucleosome, thereby ensuring that Set2 targets specifically on the reassembling upstream nucleosome. Cryo–electron microscopy structures of the nucleosome-transcribing EC complexed with Set2 revealed that Set2 is anchored by the Spt6 subunit of the EC to capture both of the H3 N-terminal tails in a stepwise manner during the nucleosome reassembly process. Abrogation of the Set2-EC interaction leads to defective transcription-coupled H3K36me3 deposition. These insights elucidate the structure-based mechanism of transcription-coupled H3K36me3 deposition in chromatin.
