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Cited by 61Genomics and Chromatin DynamicsDiffusion and Search DynamicsPluripotent Stem Cells Research

Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors

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Li, Sai, Zheng, Eric Bo, Zhao, Li, Liu, Shixin·2019·Cell Reports
DOI 10.1016/j.celrep.2019.07.103PMC PMC6750763

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Abstract

Cooperative binding of transcription factors (TFs) to chromatin orchestrates gene expression programming and cell fate specification. However, the biophysical principles of TF cooperativity remain incompletely understood. Here we use single-molecule fluorescence microscopy to study the partnership between Sox2 and Oct4, two core members of the pluripotency gene regulatory network. We find that the ability of Sox2 to target DNA inside nucleosomes is strongly affected by the translational and rotational positioning of its binding motif. In contrast, Oct4 can access nucleosomal sites with equal capacities. Furthermore, the Sox2-Oct4 pair displays nonreciprocal cooperativity, with Oct4 modulating interaction of Sox2 with the nucleosome but not vice versa. Such cooperativity is conditional upon the composite motif's residing at specific nucleosomal locations. These results reveal that pioneer factors possess distinct chromatin-binding properties and suggest that the same set of TFs can differentially regulate gene activities on the basis of their motif positions in the nucleosomal context.

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  • The pioneering model of reprogramming has been proposed for OSKM based on their ability to bind to chromatin not normally accessible by transcription factors.

    “The pioneering model of reprogramming has been proposed for OSKM based on their ability to bind to chromatin not normally accessible by transcription factors60–62.”

    From The NuRD complex cooperates with SALL4 to orchestrate reprogramming (2023) · cites this paper as [61]

    The Introduction (page unavailable) says Sox2, Oct4, and Klf4 can bind nucleosomes and silent, DNase-resistant chromatin, supporting the proposed pioneering model for those factors. It explicitly excludes c-Myc, so the claim overextends that ability to all four OSKM factors. (LLM, conf=0.90)

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Cited by

Sorted by citations

Authors
Li, S., Zheng, E. B., Zhao, L., & Liu, S.
Affiliations
Rockefeller University (US)
Corresponding author
Liu, Shixin
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2019-09
Volume
28
Issue
10
Pages
2689-2703.e4
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2019.07.103
PMC
PMC6750763
OpenAlex
W2971747719
Cited by
61
References
5
Citations by year
2026: 4 · 2025: 10 · 2024: 9 · 2023: 3 · 2022: 16 · 2021: 6 · 2020: 11 · 2019: 2
FWCI
2.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • March of Dimes Foundation (5-FY17-61)
  • National Institutes of Health (T32GM007739)
  • Alfred P. Sloan Foundation (FG-2018-10627)
  • Robertson Foundation
  • Sidney Kimmel Foundation
  • Monique Weill-Caulier Trust
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 › Pluripotent Stem Cells Research
Keywords
transcription factor cooperativity, SOX2, Oct4, pluripotency transcription factors, pioneer factors, nucleosome binding, chromatin accessibility, single-molecule fluorescence microscopy, gene regulatory networks
MeSH terms
Single Molecule Imaging, Binding Sites, DNA, HeLa Cells, Humans, Kinetics, Nucleosomes, Protein Binding, RNA, Pluripotent Stem Cells, Octamer Transcription Factor-3, SOXB1 Transcription Factors, Genetic Loci, Nucleotide Motifs

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