8G87

Human Oct4 bound to nucleosome with human nMatn1 sequence (focused refinement of Oct4 bound region)

8G87 の概要

• エントリーDOI: 10.2210/pdb8g87/pdb
• 関連するPDBエントリー: 8G86 8G88 8G8B 8G8E 8G8G
• EMDBエントリー: 29837 29841 29843 29845 29846 29850
• 分子名称: nMatn1 DNA (top strand), nMatn1 DNA (bottom strand), POU domain, class 5, transcription factor 1 (3 entities in total)
• 機能のキーワード: oct4, nucleosome, pioneer factor, nmatn1 dna, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 157122.90

構造登録者

Sinha, K.K.,Bilokapic, S.,Du, Y.,Malik, D.,Halic, M. (登録日: 2023-02-17, 公開日: 2023-03-22, 最終更新日: 2024-06-19)

主引用文献

Sinha, K.K.,Bilokapic, S.,Du, Y.,Malik, D.,Halic, M.
Histone modifications regulate pioneer transcription factor cooperativity.
Nature, 619:378-384, 2023

PubMed Abstract: Pioneer transcription factors have the ability to access DNA in compacted chromatin. Multiple transcription factors can bind together to a regulatory element in a cooperative way, and cooperation between the pioneer transcription factors OCT4 (also known as POU5F1) and SOX2 is important for pluripotency and reprogramming. However, the molecular mechanisms by which pioneer transcription factors function and cooperate on chromatin remain unclear. Here we present cryo-electron microscopy structures of human OCT4 bound to a nucleosome containing human LIN28B or nMATN1 DNA sequences, both of which bear multiple binding sites for OCT4. Our structural and biochemistry data reveal that binding of OCT4 induces changes to the nucleosome structure, repositions the nucleosomal DNA and facilitates cooperative binding of additional OCT4 and of SOX2 to their internal binding sites. The flexible activation domain of OCT4 contacts the N-terminal tail of histone H4, altering its conformation and thus promoting chromatin decompaction. Moreover, the DNA-binding domain of OCT4 engages with the N-terminal tail of histone H3, and post-translational modifications at H3K27 modulate DNA positioning and affect transcription factor cooperativity. Thus, our findings suggest that the epigenetic landscape could regulate OCT4 activity to ensure proper cell programming.

PubMed: 37225990
DOI: 10.1038/s41586-023-06112-6

実験手法

ELECTRON MICROSCOPY (8.1 Å)