8BVW

RNA polymerase II pre-initiation complex with the distal +1 nucleosome (PIC-Nuc18W)

This is a non-PDB format compatible entry.

Summary for 8BVW

• Entry DOI: 10.2210/pdb8bvw/pdb
• Related: 8BYQ 8BZ1
• EMDB information: 16274 16331 16335 16365 16366 16367 16368 16369
• Descriptor: General transcription and DNA repair factor IIH helicase subunit XPB, Cyclin-H, DNA-directed RNA polymerase subunit, ... (41 entities in total)
• Functional Keywords: mammalian pic, +1 nucleosome, transcription initiation, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 42
• Total formula weight: 1550717.72

Authors

Abril-Garrido, J.,Dienemann, C.,Grabbe, F.,Velychko, T.,Lidschreiber, M.,Wang, H.,Cramer, P. (deposition date: 2022-12-20, release date: 2023-05-03, Last modification date: 2024-07-24)

Primary citation

Abril-Garrido, J.,Dienemann, C.,Grabbe, F.,Velychko, T.,Lidschreiber, M.,Wang, H.,Cramer, P.
Structural basis of transcription reduction by a promoter-proximal +1 nucleosome.
Mol.Cell, 83:1798-, 2023

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 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.

PubMed: 37148879
DOI: 10.1016/j.molcel.2023.04.011

Experimental method

ELECTRON MICROSCOPY (4 Å)