7NL0

Cryo-EM structure of the Lin28B nucleosome core particle

7NL0 の概要

• エントリーDOI: 10.2210/pdb7nl0/pdb
• EMDBエントリー: 12453
• 分子名称: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (6 entities in total)
• 機能のキーワード: reprogramming, oct4 binding sites, nucleosome, gene regulation
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 209858.79

構造登録者

Roberts, G.A.,Ozkan, B.,Gachulincova, I.,O Dwyer, M.R.,Hall-Ponsele, E.,Saxena, M.,Robinson, P.J.,Soufi, A. (登録日: 2021-02-19, 公開日: 2021-08-11, 最終更新日: 2024-07-10)

主引用文献

Roberts, G.A.,Ozkan, B.,Gachulincova, I.,O'Dwyer, M.R.,Hall-Ponsele, E.,Saxena, M.,Robinson, P.J.,Soufi, A.
Dissecting OCT4 defines the role of nucleosome binding in pluripotency.
Nat.Cell Biol., 23:834-845, 2021

PubMed Abstract: Pioneer transcription factors such as OCT4 can target silent genes embedded in nucleosome-dense regions. How nucleosome interaction enables transcription factors to target chromatin and determine cell identity remains elusive. Here, we systematically dissect OCT4 to show that nucleosome binding is encoded within the DNA-binding domain and yet can be uncoupled from free-DNA binding. Furthermore, accelerating the binding kinetics of OCT4 to DNA enhances nucleosome binding. In cells, uncoupling nucleosome binding diminishes the ability of OCT4 to individually access closed chromatin, while more dynamic nucleosome binding results in expansive genome scanning within closed chromatin. However, both uncoupling and enhancing nucleosome binding are detrimental to inducing pluripotency from differentiated cells. Remarkably, stable interactions between OCT4 and nucleosomes are continuously required for maintaining the accessibility of pluripotency enhancers in stem cells. Our findings reveal how the affinity and residence time of OCT4-nucleosome complexes modulate chromatin accessibility during cell fate changes and maintenance.

PubMed: 34354236
DOI: 10.1038/s41556-021-00727-5

実験手法

ELECTRON MICROSCOPY (3.5 Å)