Related Experiment Video

Updated: Aug 10, 2025

Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
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Structural mechanism of LIN28B nucleosome targeting by OCT4 for pluripotency

Ruifang Guan1,2, Tengfei Lian1,2, Bing-Rui Zhou1

  • 1Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Biorxiv : the Preprint Server for Biology
|February 15, 2023
PubMed

Insights

Pioneer transcription factors like OCT4 reprogram cells by binding nucleosomal DNA. This study reveals OCT4

Area of Science:

  • * Molecular Biology
  • * Structural Biology
  • * Epigenetics

Background:

  • * Pioneer transcription factors are crucial for cell fate determination and reprogramming, enabling access to closed chromatin.
  • * OCT4 is a key pioneer factor with reprogramming capabilities, but the structural mechanisms of its interaction with nucleosomal DNA targets in vivo remain unclear.

Approach:

  • * Determined high-resolution structures of nucleosomes containing human LIN28B DNA and their complexes with the OCT4 DNA-binding region.
  • * Utilized biochemical studies to investigate the cooperative opening of H1-condensed nucleosome arrays by multiple OCT4 molecules.

Key Points:

  • * Three OCT4 molecules bind a pre-positioned nucleosome, recognizing non-canonical DNA motifs.
  • * Two OCT4 molecules utilize their POUS domains for extensive hydrogen bonding.
  • * A third OCT4 molecule employs its POUS-loop-POUHD region, with POUHD acting as a wedge to unwrap approximately 25 base pairs of DNA.

Conclusions:

  • * OCT4 targets the LIN28B nucleosome through multivalent interactions, DNA unwrapping, and H1 eviction.
  • * Multiple OCT4 molecules cooperatively open closed chromatin, providing a mechanism for initiating cell reprogramming.

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