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-Structure paper
| タイトル | Molecular mechanism of co-transcriptional H3K36 methylation by SETD2. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 9565, Year 2025 |
| 掲載日 | 2025年10月29日 |
著者 | James L Walshe / Moritz Ochmann / Ute Neef / Olexandr Dybkov / Christian Dienemann / Christiane Oberthür / Aiturgan Zheenbekova / Henning Urlaub / Patrick Cramer / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:41162378 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.58 - 6.72 Å |
| 構造データ | EMDB-51643, PDB-9gw2: EMDB-54247, PDB-9rtn: EMDB-54399, PDB-9rzc: EMDB-54400, PDB-9rzd: EMDB-54425, PDB-9s0u: EMDB-54537, PDB-9s3g: ![]() EMDB-54538: State 1 MAP1 RNA Pol II activated elongation complex with SETD2 and upstream hexasome ![]() EMDB-54541: State 1 MAP2 RNA Pol II activated elongation complex with SETD2 and upstream hexasome ![]() EMDB-54542: State 1 MAP4 RNA Pol II activated elongation complex with SETD2 and upstream hexasome |
| 化合物 | ![]() ChemComp-ZN: ![]() ChemComp-MG: |
| 由来 |
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キーワード | TRANSCRIPTION / RNA Pol II Activated elongation complex Co-transcriptional H3K36me3 SETD2 |
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