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TitleStructural mechanism of LIN28B nucleosome targeting by OCT4.
Journal, issue, pagesMol Cell, Vol. 83, Issue 12, Page 1970-11982.e6, Year 2023
Publish dateJun 15, 2023
AuthorsRuifang Guan / Tengfei Lian / Bing-Rui Zhou / David Wheeler / Yawen Bai /
PubMed AbstractPioneer 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 ...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.
External linksMol Cell / PubMed:37327775 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 7.9 Å
Structure data

EMDB-26258, PDB-7u0g:
structure of LIN28b nucleosome bound 3 OCT4
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-26260, PDB-7u0i:
Structure of LIN28b nucleosome bound 2 OCT4
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-26261, PDB-7u0j:
Structure of 162bp LIN28b nucleosome
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-27483, PDB-8dk5:
Structure of 187bp LIN28b nucleosome with site 0 mutation
Method: EM (single particle) / Resolution: 2.71 Å

EMDB-40683, PDB-8sps:
High resolution structure of ESRRB nucleosome bound OCT4 at site a and site b
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-40684: Low resolution reconstruction of ESRRB nucleosome bound OCT4 at site a and site b
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-40686, PDB-8spu:
Structure of ESRRB nucleosome bound OCT4 at site c
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-40691: Focused classification of site c OCT4
Method: EM (single particle) / Resolution: 7.9 Å

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
  • escherichia coli (E. coli)
  • escherichia coli k-12 (bacteria)
KeywordsTRANSCRIPTION/DNA / nucleosome / transcription factor / transcription / CHROMATIN BINDING PROTEIN-DNA complex / TRANSCRIPTION-DNA complex / GENE REGULATION

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