Cell fate control by pioneer transcription factors
Open accessAbstract
Distinct combinations of transcription factors are necessary to elicit cell fate changes in embryonic development. Yet within each group of fate-changing transcription factors, a subset called 'pioneer factors' are dominant in their ability to engage silent, unmarked chromatin and initiate the recruitment of other factors, thereby imparting new function to regulatory DNA sequences. Recent studies have shown that pioneer factors are also crucial for cellular reprogramming and that they are implicated in the marked changes in gene regulatory networks that occur in various cancers. Here, we provide an overview of the contexts in which pioneer factors function, how they can target silent genes, and their limitations at regions of heterochromatin. Understanding how pioneer factors regulate gene expression greatly enhances our understanding of how specific developmental lineages are established as well as how cell fates can be manipulated.
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Some developmental TFs can reprogram one cell type into another by engaging developmentally silent genes in closed chromatin, acting as pioneer TFs.
“Some developmental TFs have the remarkable ability to reprogram one cell type into another by engaging genes that are developmentally silent and in closed chromatin, thus acting as pioneer TFs to initiate transcriptional events (21).”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [21]
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- Authors
- Iwafuchi-Doi, M., & Zaret, K. S.
- Affiliations
- Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, 9-131 SCTR, 3400 Civic Center Blvd., Philadelphia, PA 19104-5157, USA
- University of Pennsylvania (US)
- ORCID
- Zaret, Kenneth S.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2016-06-01
- Volume
- 143
- Issue
- 11
- Pages
- 1833-1837
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC6514407
- OpenAlex
- W2418343927
- Cited by
- 304
- References
- 8
- Citations by year
- 2026: 24 · 2025: 15 · 2024: 26 · 2023: 37 · 2022: 41 · 2021: 41 · 2020: 28 · 2019: 34 · 2018: 31 · 2017: 20 · 2016: 5 · 2015: 1
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (100000002)
- Japan Society for the Promotion of Science (501100001691)
- Naito Foundation (100007428)
- Astellas Foundation for Research on Metabolic Disorders (501100007263)
- Uehara Foundation (not in registry)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- pioneer transcription factors, cell fate determination, chromatin accessibility, silent chromatin, heterochromatin, cellular reprogramming, gene regulatory networks, cancer, embryonic development, lineage specification, transcriptional regulation
- MeSH terms
- Animals, Humans, Neoplasms, Transcription Factors, Cell Lineage, Embryonic Development
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