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Title | Structural basis of transcription reduction by a promoter-proximal +1 nucleosome. |
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Journal, issue, pages | Mol Cell, Vol. 83, Issue 11, Page 1798-11809.e7, Year 2023 |
Publish date | Jun 1, 2023 |
Authors | Julio Abril-Garrido / Christian Dienemann / Frauke Grabbe / Taras Velychko / Michael Lidschreiber / Haibo Wang / Patrick Cramer / |
PubMed Abstract | At active human genes, the +1 nucleosome is located downstream of the RNA polymerase II (RNA Pol II) pre-initiation complex (PIC). However, at inactive genes, the +1 nucleosome is found further ...At active human genes, the +1 nucleosome is located downstream of the RNA polymerase II (RNA Pol II) pre-initiation complex (PIC). However, at inactive genes, the +1 nucleosome is found further upstream, at a promoter-proximal location. Here, we establish a model system to show that a promoter-proximal +1 nucleosome can reduce RNA synthesis in vivo and in vitro, and we analyze its structural basis. We find that the PIC assembles normally when the edge of the +1 nucleosome is located 18 base pairs (bp) downstream of the transcription start site (TSS). However, when the nucleosome edge is located further upstream, only 10 bp downstream of the TSS, the PIC adopts an inhibited state. The transcription factor IIH (TFIIH) shows a closed conformation and its subunit XPB contacts DNA with only one of its two ATPase lobes, inconsistent with DNA opening. These results provide a mechanism for nucleosome-dependent regulation of transcription initiation. |
External links | Mol Cell / PubMed:37148879 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.0 - 4.5 Å |
Structure data | EMDB-16274, PDB-8bvw: EMDB-16331, PDB-8byq: EMDB-16335, PDB-8bz1: EMDB-16336: RNA polymerase II core pre-initiation complex focused map EMDB-16337: Proximal +1 nucleosome focused map EMDB-16338: RNA polymerase II core pre-initiation complex with the proximal +1 nucleosome composite map EMDB-16339: RNA polymerase II core pre-initiation complex focused map EMDB-16340: Proximal +1 nucleosome focused map EMDB-16341: TFIIH subcomplex CDK-activating kinase module focused map EMDB-16342: General transcription factor IIH in closed conformation focused map EMDB-16343: RNA polymerase II pre-initiation complex with the proximal +1 nucleosome composite map EMDB-16365: RNA polymerase II core pre-initiation complex focused map EMDB-16366: Distal +1 nucleosome focused map EMDB-16367: General transcription factor IIH in open conformation focused map EMDB-16368: TFIIH subcomplex CDK-activating kinase module focused map EMDB-16369: RNA polymerase II pre-initiation complex with the distal +1 nucleosome composite map |
Chemicals | ChemComp-SF4: ChemComp-ZN: ChemComp-MG: |
Source |
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Keywords | TRANSCRIPTION / Mammalian PIC / +1 nucleosome / transcription initiation |