8SPU

Structure of ESRRB nucleosome bound OCT4 at site c

Summary for 8SPU

• Entry DOI: 10.2210/pdb8spu/pdb
• EMDB information: 40683 40684 40686 40691
• Descriptor: DNA (168-MER), Maltodextrin-binding protein,POU domain, class 5, transcription factor 1, Histone H3.1, ... (8 entities in total)
• Functional Keywords: nucleosome, transcription factor, transcription, chromatin binding protein-dna complex, gene regulation, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 13
• Total formula weight: 332670.59

Authors

Lian, T.,Guan, R.,Bai, Y. (deposition date: 2023-05-03, release date: 2023-06-28, Last modification date: 2024-10-16)

Primary citation

Guan, R.,Lian, T.,Zhou, B.R.,Wheeler, D.,Bai, Y.
Structural mechanism of LIN28B nucleosome targeting by OCT4.
Mol.Cell, 83:1970-1982.e6, 2023

PubMed Abstract: Pioneer transcription factors are essential for cell fate changes by targeting closed chromatin. OCT4 is a crucial pioneer factor that can induce cell reprogramming. However, the structural basis of how pioneer factors recognize the in vivo nucleosomal DNA targets is unknown. Here, we determine the high-resolution structures of the nucleosome containing human LIN28B DNA and its complexes with the OCT4 DNA binding region. Three OCT4s bind the pre-positioned nucleosome by recognizing non-canonical DNA sequences. Two use their POUS domains while the other uses the POUS-loop-POUHD region; POUHD serves as a wedge to unwrap ∼25 base pair DNA. Our analysis of previous genomic data and determination of the ESRRB-nucleosome-OCT4 structure confirmed the generality of these structural features. Moreover, biochemical studies suggest that multiple OCT4s cooperatively open the H1-condensed nucleosome array containing the LIN28B nucleosome. Thus, our study suggests a mechanism of how OCT4 can target the nucleosome and open closed chromatin.

PubMed: 37327775
DOI: 10.1016/j.molcel.2023.05.030

Experimental method

ELECTRON MICROSCOPY (2.8 Å)