7SSA

Cryo-EM structure of pioneer factor Cbf1 bound to the nucleosome

Summary for 7SSA

• Entry DOI: 10.2210/pdb7ssa/pdb
• EMDB information: 25406
• Descriptor: Histone H3.2, Histone H4, Histone H2A.1, ... (7 entities in total)
• Functional Keywords: transcription factor, basic helix-loop-helix, complex, gene regulation
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 12
• Total formula weight: 280357.92

Authors

Eek, P.,Tan, S. (deposition date: 2021-11-10, release date: 2023-04-05, Last modification date: 2024-06-05)

Primary citation

Donovan, B.T.,Chen, H.,Eek, P.,Meng, Z.,Jipa, C.,Tan, S.,Bai, L.,Poirier, M.G.
Basic helix-loop-helix pioneer factors interact with the histone octamer to invade nucleosomes and generate nucleosome-depleted regions.
Mol.Cell, 83:1251-1263.e6, 2023

PubMed Abstract: Nucleosomes drastically limit transcription factor (TF) occupancy, while pioneer transcription factors (PFs) somehow circumvent this nucleosome barrier. In this study, we compare nucleosome binding of two conserved S. cerevisiae basic helix-loop-helix (bHLH) TFs, Cbf1 and Pho4. A cryo-EM structure of Cbf1 in complex with the nucleosome reveals that the Cbf1 HLH region can electrostatically interact with exposed histone residues within a partially unwrapped nucleosome. Single-molecule fluorescence studies show that the Cbf1 HLH region facilitates efficient nucleosome invasion by slowing its dissociation rate relative to DNA through interactions with histones, whereas the Pho4 HLH region does not. In vivo studies show that this enhanced binding provided by the Cbf1 HLH region enables nucleosome invasion and ensuing repositioning. These structural, single-molecule, and in vivo studies reveal the mechanistic basis of dissociation rate compensation by PFs and how this translates to facilitating chromatin opening inside cells.

PubMed: 36996811
DOI: 10.1016/j.molcel.2023.03.006

Experimental method

ELECTRON MICROSCOPY (3.2 Å)