9RTN

State 2 MAP 2 SPT6 with SETD2

9RTN の概要

• エントリーDOI: 10.2210/pdb9rtn/pdb
• 関連するPDBエントリー: 9GW2
• EMDBエントリー: 54247
• 分子名称: RNA polymerase II subunit D, DNA-directed RNA polymerase II subunit RPB7, Histone-lysine N-methyltransferase SETD2, ... (5 entities in total)
• 機能のキーワード: rna pol ii activated elongation complex co-transcriptional h3k36me3 setd2, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 484281.31

構造登録者

Walshe, J.L.,Ochmann, M.,Dienemann, C.,Cramer, P. (登録日: 2025-07-03, 公開日: 2025-09-24, 最終更新日: 2025-11-12)

主引用文献

Walshe, J.L.,Ochmann, M.,Neef, U.,Dybkov, O.,Dienemann, C.,Oberthur, C.,Zheenbekova, A.,Urlaub, H.,Cramer, P.
Molecular mechanism of co-transcriptional H3K36 methylation by SETD2.
Nat Commun, 16:9565-9565, 2025

PubMed Abstract: H3K36me3 is a hallmark of actively and recently transcribed genes and contributes to cellular memory and identity. The deposition of H3K36me3 occurs co-transcriptionally when the methyltransferase SETD2 associates with RNA polymerase II. Here we present three cryo-EM structures of SETD2 bound to RNA polymerase II elongation complexes at different states of nucleosome passage. Together with functional probing, our results suggest a 3-step mechanism of transcription-coupled H3K36me3 deposition. First, binding to the elongation factor SPT6 tethers the catalytic SET domain in proximity to the upstream DNA. Second, RNA polymerase II nucleosome passage leads to the transfer of a hexasome from downstream to upstream, poised for methylation. Finally, continued transcription leads to upstream nucleosome reassembly, partial dissociation of the histone chaperone FACT and sequential methylation of both H3 tails, completing H3K36me3 deposition of an upstream nucleosome after RNA polymerase II passage.

PubMed: 41162378
DOI: 10.1038/s41467-025-65439-y

実験手法

ELECTRON MICROSCOPY (3.82 Å)