8EVH

CX3CR1 nucleosome and wild type PU.1 complex

Summary for 8EVH

• Entry DOI: 10.2210/pdb8evh/pdb
• EMDB information: 28629
• Descriptor: Histone H3.1, Histone H4, Histone H2A type 2-C, ... (8 entities in total)
• Functional Keywords: nucleosome, transcription factor, transcription, chromatin binding protein-dna complex, dna binding protein-dna complex, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 13
• Total formula weight: 300490.37

Authors

Lian, T.,Guan, R.,Bai, Y. (deposition date: 2022-10-20, release date: 2023-11-01, Last modification date: 2024-10-16)

Primary citation

Lian, T.,Guan, R.,Zhou, B.R.,Bai, Y.
Structural mechanism of synergistic targeting of the CX3CR1 nucleosome by PU.1 and C/EBP alpha.
Nat.Struct.Mol.Biol., 31:633-643, 2024

PubMed Abstract: Pioneer transcription factors are vital for cell fate changes. PU.1 and C/EBPα work together to regulate hematopoietic stem cell differentiation. However, how they recognize in vivo nucleosomal DNA targets remains elusive. Here we report the structures of the nucleosome containing the mouse genomic CX3CR1 enhancer DNA and its complexes with PU.1 alone and with both PU.1 and the C/EBPα DNA binding domain. Our structures reveal that PU.1 binds the DNA motif at the exit linker, shifting 17 bp of DNA into the core region through interactions with H2A, unwrapping ~20 bp of nucleosomal DNA. C/EBPα binding, aided by PU.1's repositioning, unwraps ~25 bp of entry DNA. The PU.1 Q218H mutation, linked to acute myeloid leukemia, disrupts PU.1-H2A interactions. PU.1 and C/EBPα jointly displace linker histone H1 and open the H1-condensed nucleosome array. Our study unveils how two pioneer factors can work cooperatively to open closed chromatin by altering DNA positioning in the nucleosome.

PubMed: 38267599
DOI: 10.1038/s41594-023-01189-z

Experimental method

ELECTRON MICROSCOPY (2.85 Å)