7ssa

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

Structural highlights

7ssa is a 12 chain structure with sequence from Saccharomyces cerevisiae S288C, Xenopus laevis and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

H32_XENLA Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

Publication Abstract from PubMed

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.

Basic helix-loop-helix pioneer factors interact with the histone octamer to invade nucleosomes and generate nucleosome-depleted regions.,Donovan BT, Chen H, Eek P, Meng Z, Jipa C, Tan S, Bai L, Poirier MG Mol Cell. 2023 Apr 20;83(8):1251-1263.e6. doi: 10.1016/j.molcel.2023.03.006. Epub , 2023 Mar 29. PMID:36996811^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Donovan BT, Chen H, Eek P, Meng Z, Jipa C, Tan S, Bai L, Poirier MG. Basic helix-loop-helix pioneer factors interact with the histone octamer to invade nucleosomes and generate nucleosome-depleted regions. Mol Cell. 2023 Apr 20;83(8):1251-1263.e6. PMID:36996811 doi:10.1016/j.molcel.2023.03.006

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OCA

[1] Donovan BT, Chen H, Eek P, Meng Z, Jipa C, Tan S, Bai L, Poirier MG. Basic helix-loop-helix pioneer factors interact with the histone octamer to invade nucleosomes and generate nucleosome-depleted regions. Mol Cell. 2023 Apr 20;83(8):1251-1263.e6. PMID:36996811 doi:10.1016/j.molcel.2023.03.006

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