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Structural mechanism of LIN28B nucleosome targeting by OCT4.

Authors :
Guan, Ruifang
Lian, Tengfei
Zhou, Bing-Rui
Wheeler, David
Bai, Yawen
Source :
Molecular Cell. Jun2023, Vol. 83 Issue 12, p1970-1970. 1p.
Publication Year :
2023

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. [Display omitted] • High-resolution structures of the LIN28B nucleosome bound to three OCT4s • All OCT4s recognize non-canonical DNA sequences in the nucleosome • One OCT4 POUHD serves as a wedge to unwrap ∼25 bp nucleosomal DNA • OCT4s work cooperatively to open H1-condensed nucleosome array Guan et al. determined the structures of the nucleosome containing a genomic DNA and its complexes with OCT4. They find that multiple OCT4 molecules bind the nucleosome and its two DNA binding domains work together to unwrap the nucleosomal DNA. The study suggests how OCT4 may open closed chromatin locally. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10972765
Volume :
83
Issue :
12
Database :
Academic Search Index
Journal :
Molecular Cell
Publication Type :
Academic Journal
Accession number :
164249416
Full Text :
https://doi.org/10.1016/j.molcel.2023.05.030