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.
EMDB-63816, PDB-9u3k: Glycogen phosphorylase from Segatella copri pentamer in complex with AMP chains D and E Method: EM (single particle) / Resolution: 3.32 Å
EMDB-64926, PDB-9vbl: Cryo-EM structure of glycogen phosphorylase from Dorea longicatena (monomer form) Method: EM (single particle) / Resolution: 3.39 Å
EMDB-64927, PDB-9vbm: Cryo-EM structure of glycogen phosphorylase from Dorea longicatena (dimer form) Method: EM (single particle) / Resolution: 3.19 Å
EMDB-64931: Cryo-EM map of glycogen phosphorylase from Dorea longicatena (monomer form with extra density) Method: EM (single particle) / Resolution: 3.3 Å
EMDB-65042: Glycogen phosphorylase dimer from E. coli in complex with glycogen Method: EM (single particle) / Resolution: 3.46 Å
EMDB-66103, PDB-9wms: Co-transcriptional histone H3K36 methylation complex containing RNA polymerase II elongation complex, Set2, and the upstream nucleosome. (temp115, type B) Method: EM (single particle) / Resolution: 3.4 Å
EMDB-66104, PDB-9wmt: Co-transcriptional histone H3K36 methylation complex containing RNA polymerase II elongation complex, Set2, and the upstream nucleosome. (temp115, type A) Method: EM (single particle) / Resolution: 3.59 Å
EMDB-66105, PDB-9wmu: Co-transcriptional histone H3K36 methylation complex containing RNA polymerase II elongation complex, Set2, and the upstream nucleosome. (temp130, type A) Method: EM (single particle) / Resolution: 4.28 Å
EMDB-66106, PDB-9wmv: Co-transcriptional histone H3K36 methylation complex containing RNA polymerase II elongation complex, Set2, and the upstream nucleosome. (temp130, type B) Method: EM (single particle) / Resolution: 4.66 Å
EMDB-67418, PDB-20ys: R583A mutant of glycogen phosphorylase from Segatella copri in the presence of AMP Method: EM (single particle) / Resolution: 2.96 Å
PDB-9maq: Glycogen phosphorylase from D. longicatena Method: X-RAY DIFFRACTION / Resolution: 3.8 Å
PDB-9ukq: Crystal structure of glycogen phosphorylase from Escherichia coli Method: X-RAY DIFFRACTION / Resolution: 3.5 Å
PDB-9ukr: Crystal structure of glycogen phosphorylase from E. coli in complex with AMP Method: X-RAY DIFFRACTION / Resolution: 3.55 Å
PDB-9v16: Crystal structure of E. coli glycogen phosphorylase N185A/R267E mutant in complex with AMP Method: X-RAY DIFFRACTION / Resolution: 3.45 Å
PDB-9v17: Crystal structure of E. coli glycogen phosphorylase N185A/R267E mutant Method: X-RAY DIFFRACTION / Resolution: 3.7 Å
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