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| Title | Structural basis of H3K36 trimethylation by SETD2 during chromatin transcription. |
|---|---|
| Journal, issue, pages | Science, Page eadn6319, Year 2024 |
| Publish date | Dec 12, 2024 |
 Authors | Jonathan W Markert / Jelly H Soffers / Lucas Farnung /  |
| PubMed Abstract | During transcription, RNA polymerase II traverses through chromatin, and post-translational modifications including histone methylations mark regions of active transcription. Histone protein H3 ...During transcription, RNA polymerase II traverses through chromatin, and post-translational modifications including histone methylations mark regions of active transcription. Histone protein H3 lysine 36 trimethylation (H3K36me3), which is established by the histone methyltransferase SETD2, suppresses cryptic transcription, regulates splicing, and serves as a binding site for transcription elongation factors. The mechanism by which the transcription machinery coordinates the deposition of H3K36me3 is not well understood. Here we provide cryo-electron microscopy structures of mammalian RNA polymerase II-DSIF-SPT6-PAF1c-TFIIS-IWS1-SETD2-nucleosome elongation complexes, revealing that the transcription machinery regulates H3K36me3 deposition by SETD2 on downstream and upstream nucleosomes. SPT6 binds the exposed H2A-H2B dimer during transcription and the SPT6 death-like domain mediates an interaction with SETD2 bound to a nucleosome upstream of RNA polymerase II. |
 External links | Science / PubMed:39666822 |
| Methods | EM (single particle) |
| Resolution | 2.9 - 12.1 Å |
| Structure data |  EMDB-48019: map 5 SETD2 nucleosome  EMDB-48020: map6 SETD2 AID  EMDB-48021: map 7 SETD2-SPT6 nucleosome  EMDB-48022: map 8 Full upstream  EMDB-48023: map Alpha RNA Polymerase II  EMDB-48025: map gamma SPT6  EMDB-48026: map delta IWS1  EMDB-48027: map epsilon SETD2 nucleosome  EMDB-48028: map Zeta SETD2-SPT6 nucleosome  EMDB-48029: map Eta full upstream  EMDB-48030: map I FACT-RNA Polymerase II upstream complex  EMDB-48031: map II FACT upstream focused  EMDB-48032: map III SPT6 focused  EMDB-48033: map IV PAF1C EMDB-48039, PDB-9egx: EMDB-48040, PDB-9egy: EMDB-48041, PDB-9egz: EMDB-48042, PDB-9eh0: EMDB-48043, PDB-9eh1: EMDB-48044, PDB-9eh2: |
| Chemicals |  ChemComp-ZN:  ChemComp-MG: |
| Source |
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 Keywords | TRANSCRIPTION / TRANSFERASE/RNA/DNA / SETD2 / H3K36me3 / TRANSFERASE-RNA-DNA complex |
homo sapiens (human)
sus scrofa (pig)
xenopus laevis (African clawed frog)