Japan Agency for Medical Research and Development (AMED)
JP24ama121009
Japan
Japan Society for the Promotion of Science (JSPS)
JP20H05690
Japan
Japan Society for the Promotion of Science (JSPS)
JP24H00062
Japan
Japan Society for the Promotion of Science (JSPS)
JP20H03201
Japan
Japan Society for the Promotion of Science (JSPS)
JP23K17392
Japan
Japan Society for the Promotion of Science (JSPS)
JP22K15033
Japan
Japan Society for the Promotion of Science (JSPS)
JP24H02328
Japan
Japan Society for the Promotion of Science (JSPS)
JP23H05475
Japan
Japan Society for the Promotion of Science (JSPS)
JP20H05906
Japan
Japan Science and Technology
JPMJER1901
Japan
Japan Science and Technology
JPMJCR24T3
Japan
Other private
Daiichi Sankyo Foundation for Life Science
Citation
Journal: Sci Adv / Year: 2026 Title: Structural basis of transcription-coupled H3K36 trimethylation by Set2 in coordination with FACT. Authors: Tomoya Kujirai / Haruhiko Ehara / Tomoko Ito / Masami Henmi / Eriko Oya / Takehiko Kobayashi / Shun-Ichi Sekine / Hitoshi Kurumizaka / Abstract: Trimethylation of the histone H3K36 residue (H3K36me3) plays an indispensable role in ensuring transcription fidelity by suppressing undesired cryptic transcription in chromatin. H3K36me3 ...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.
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