8UBL

Cryo-EM structure of Ascl1/E12a in complex with NRCAM nucleosome (3D Flex map)

Summary for 8UBL

• Entry DOI: 10.2210/pdb8ubl/pdb
• EMDB information: 42094
• Descriptor: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (9 entities in total)
• Functional Keywords: nucleosome, pioneer transcription factors, dna binding proteins, transcription, nuclear protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 16
• Total formula weight: 453657.27

Authors

Zhou, B.R.,Bai, Y. (deposition date: 2023-09-23, release date: 2026-01-21, Last modification date: 2026-06-24)

Primary citation

Zhou, B.R.,Luzete-Monteiro, E.,Zhang, J.,Takenaka, N.,Tang, H.Y.,Fernandez Garcia, M.,Coradin, M.,Frederick, M.,Donahue, G.,Garcia, B.,Bai, Y.,Zaret, K.S.
Distinct associations of pioneer factor Ascl1-E12a with nucleosomes drive changes in cell fate.
Mol.Cell, 2026

PubMed Abstract: Understanding how pioneer transcription factors target nucleosomal DNA and initiate chromatin accessibility reveals the earliest events in cell fate changes. We integrated structural, biochemical, and genomic approaches to assess how the pioneer factor Ascl1-E12a heterodimer perturbs nucleosomes in vitro and in vivo to induce a neural cell fate. Two Ascl1-E12a heterodimers shift and unwrap 15 bp of nucleosomal DNA in a stepwise manner while eliciting solvent exchanges within the octamer. Nucleosome binding, but not free DNA binding, by Ascl1-E12a is enhanced by two types of associations with the nucleosome that differentially affect the kinetics of DNA unwrapping and shifting. Nucleosome association mutants of Ascl1 perturb chromatin opening on linker histone-compacted nucleosome arrays-independent of nucleosome remodelers-and targeting of closed chromatin in vivo, with consequent deficiencies in cellular reprogramming. Our findings establish that distinct associations with nucleosomes are essential for the pioneer factor Ascl1 to overcome chromatin barriers to reprogram cell fate.

PubMed: 42285106
DOI: 10.1016/j.molcel.2026.05.020

Experimental method

ELECTRON MICROSCOPY (2.8 Å)