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Cited by 47Genomics and Chromatin DynamicsDiffusion and Search DynamicsEpigenetics and DNA Methylation

Nucleosome binding by the pioneer transcription factor OCT4

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Echigoya, Kenta, Koyama, Masako, Negishi, Lumi, Takizawa, Yoshimasa, Mizukami, Yuka, Shimabayashi, Hideki, Kuroda, Akari, Kurumizaka, Hitoshi·2020·Scientific Reports
DOI 10.1038/s41598-020-68850-1PMC PMC7367260
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Abstract

Transcription factor binding to genomic DNA is generally prevented by nucleosome formation, in which the DNA is tightly wrapped around the histone octamer. In contrast, pioneer transcription factors efficiently bind their target DNA sequences within the nucleosome. OCT4 has been identified as a pioneer transcription factor required for stem cell pluripotency. To study the nucleosome binding by OCT4, we prepared human OCT4 as a recombinant protein, and biochemically analyzed its interactions with the nucleosome containing a natural OCT4 target, the LIN28B distal enhancer DNA sequence, which contains three potential OCT4 target sequences. By a combination of chemical mapping and cryo-electron microscopy single-particle analysis, we mapped the positions of the three target sequences within the nucleosome. A mutational analysis revealed that OCT4 preferentially binds its target DNA sequence located near the entry/exit site of the nucleosome. Crosslinking mass spectrometry consistently showed that OCT4 binds the nucleosome in the proximity of the histone H3 N-terminal region, which is close to the entry/exit site of the nucleosome. We also found that the linker histone H1 competes with OCT4 for the nucleosome binding. These findings provide important information for understanding the molecular mechanism by which OCT4 binds its target DNA in chromatin.

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  • At least some pioneer factors, such as FOXA, OCT4 and SOX2/SOX11, initiate chromatin opening by direct displacement of histones.

    “The mechanisms of pioneer factor action are still being established [37], but at least some of them (such as FOXA, OCT4 and SOX2/SOX11) have been shown to initiate chromatin opening by direct displacement of histones [38–41], whilst many others recruit chromatin remodelers [42–50].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [39]

    The Introduction says OCT4 may help convert closed chromatin to open chromatin, but it does not attribute that opening to direct histone displacement. The Results section “Linker histone H1 competes with OCT4 for nucleosome binding” reports the opposite of the claimed mechanism for OCT4: adding OCT4 did not displace H1; adding H1 removed OCT4 from the nucleosome. The Discussion describes SOX2/SOX11 peeling DNA from histones, not displacing the histones. (LLM, conf=0.88)

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Authors
Echigoya, K., Koyama, M., Negishi, L., Takizawa, Y., Mizukami, Y., Shimabayashi, H., Kuroda, A., & Kurumizaka, H.
Affiliations
  • Institute for Quantitative Biosciences, The University of Tokyo (JP)
  • Waseda University (JP)
Corresponding author
Kurumizaka, Hitoshi
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-07-16
Volume
10
Issue
1
Pages
11832-11832
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-68850-1
PMC
PMC7367260
OpenAlex
W3042995453
Cited by
47
References
2
Citations by year
2026: 2 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 7 · 2021: 11 · 2020: 4
FWCI
2.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Japan Society for the Promotion of Science (JP18K14677, JP19K06522, JP18H05534)
  • Japan Science and Technology Agency (JPMJER1901)
  • Japan Agency for Medical Research and Development (JP20am0101076)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
Oct4, pioneer transcription factors, nucleosome binding, histone octamer, stem cell pluripotency, histone H1, chromatin
MeSH terms
Amino Acid Sequence, Base Sequence, Binding Sites, Cell-Free System, Cloning, Molecular, DNA, Enhancer Elements, Genetic, Escherichia coli, Genetic Vectors, Heterochromatin, Histones, Humans, Nucleic Acid Conformation, Nucleosomes, Protein Binding, Protein Conformation, Recombinant Fusion Proteins, Gene Expression, RNA-Binding Proteins, Protein Isoforms, Cryoelectron Microscopy, Octamer Transcription Factor-3

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