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-Structure paper
タイトル | Structural basis of transcription reduction by a promoter-proximal +1 nucleosome. |
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ジャーナル・号・ページ | Mol Cell, Vol. 83, Issue 11, Page 1798-11809.e7, Year 2023 |
掲載日 | 2023年6月1日 |
![]() | Julio Abril-Garrido / Christian Dienemann / Frauke Grabbe / Taras Velychko / Michael Lidschreiber / Haibo Wang / Patrick Cramer / ![]() |
PubMed 要旨 | 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. |
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手法 | EM (単粒子) |
解像度 | 3.0 - 4.5 Å |
構造データ | 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 |
化合物 | ![]() ChemComp-SF4: ![]() ChemComp-ZN: ![]() ChemComp-MG: |
由来 |
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![]() | TRANSCRIPTION / Mammalian PIC / +1 nucleosome / transcription initiation |