8YV8

Cryo-EM structure of CDCA7 bound to nucleosome including hemimethylated CpG site in Widom601 positioning sequence.

8YV8 の概要

• エントリーDOI: 10.2210/pdb8yv8/pdb
• EMDBエントリー: 39594
• 分子名称: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (8 entities in total)
• 機能のキーワード: nucleosome, dna methylation, cdca7, dna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 210859.56

構造登録者

Kikuchi, A.,Shikimachi, R.,Nishiyama, A.,Funabiki, H.,Arita, K. (登録日: 2024-03-28, 公開日: 2024-07-31, 最終更新日: 2025-03-12)

主引用文献

Wassing, I.E.,Nishiyama, A.,Shikimachi, R.,Jia, Q.,Kikuchi, A.,Hiruta, M.,Sugimura, K.,Hong, X.,Chiba, Y.,Peng, J.,Jenness, C.,Nakanishi, M.,Zhao, L.,Arita, K.,Funabiki, H.
CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes.
Sci Adv, 10:eadp5753-eadp5753, 2024

PubMed Abstract: Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency, centromeric instability, and facial anomalies syndrome, characterized by DNA hypomethylation at heterochromatin. It remains unclear why CDCA7-HELLS is the sole nucleosome remodeling complex whose deficiency abrogates the maintenance of DNA methylation. We here identify the unique zinc-finger domain of CDCA7 as an evolutionarily conserved hemimethylation-sensing zinc finger (HMZF) domain. Cryo-electron microscopy structural analysis of the CDCA7-nucleosome complex reveals that the HMZF domain can recognize hemimethylated CpG in the outward-facing DNA major groove within the nucleosome core particle, whereas UHRF1, the critical activator of the maintenance methyltransferase DNMT1, cannot. CDCA7 recruits HELLS to hemimethylated chromatin and facilitates UHRF1-mediated H3 ubiquitylation associated with replication-uncoupled maintenance DNA methylation. We propose that the CDCA7-HELLS nucleosome remodeling complex assists the maintenance of DNA methylation on chromatin by sensing hemimethylated CpG that is otherwise inaccessible to UHRF1 and DNMT1.

PubMed: 39178260
DOI: 10.1126/sciadv.adp5753

実験手法

ELECTRON MICROSCOPY (3 Å)