Pioneer factor pax7 deploys a stable enhancer repertoire for specification of cell fate
Abstract
Pioneer transcription factors establish new cell-fate competence by triggering chromatin remodeling. However, many features of pioneer action, such as their kinetics and stability, remain poorly defined. Here, we show that Pax7, by opening a unique repertoire of enhancers, is necessary and sufficient for specification of one pituitary lineage. Pax7 binds its targeted enhancers rapidly, but chromatin remodeling and gene activation are slower. Enhancers opened by Pax7 show a loss of DNA methylation and acquire stable epigenetic memory, as evidenced by binding of nonpioneer factors after Pax7 withdrawal. This work shows that transient Pax7 expression is sufficient for stable specification of cell identity.
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SOX9 harbours the pioneer TF ability to engage target sites in closed chromatin.
“Our results suggests that SOX9 harbours this ability but, as observed with other pioneer TFs (47,69,70), not all SOX9 binding events result in opening of chromatin.”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [47]
Dynamic chromatin binding has been observed for other pioneer TFs.
“Dynamic chromatin binding has been observed for other pioneer TFs (47) and pioneering may be viewed as a one-time event, meaning that SOX9 does not need to remain bound at sites once opened.”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [47]
Cites
Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming
Soufi, A., Garcia, M. F., Jaroszewicz, A., Osman, N., Pellegrini, M., & Zaret, K. S. (2015) · Cell · doi:10.1016/j.cell.2015.03.017 · Cited by 780 · see citing works
Voss, T. C., Schiltz, R. L., Sung, M.-H., Yen, P. M., Stamatoyannopoulos, J. A., Biddie, S. C., Johnson, T. A., Miranda, T. B., John, S., & Hager, G. L. (2011) · Cell · doi:10.1016/j.cell.2011.07.006 · Cited by 307 · see citing works
Chromatin scanning by dynamic binding of pioneer factors
Zaret, K. S., Lerner, J., & Iwafuchi-Doi, M. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.024 · Cited by 68 · see citing works
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The mechanistic basis for chromatin regulation by pioneer transcription factors
Iwafuchi‐Doi, M. (2019) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1427 · Cited by 82 · see citing works
Ponroy Bally, B., Farmer, W. T., Jones, E. V., Jessa, S., Kacerovsky, J. B., Mayran, A., Peng, H., Lefebvre, J. L., Drouin, J., Hayer, A., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa003 · Cited by 49 · see citing works
Self-citationSOX9 reprograms endothelial cells by altering the chromatin landscape
Fuglerud, B. M., Drissler, S., Lotto, J., Stephan, T. L., Thakur, A., Cullum, R., & Hoodless, P. A. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac652 · Cited by 35 · see citing works
Xu, J., Wang, L., Li, H., Yang, T., Zhang, Y., Hu, T., Huang, Z., & Chen, Y. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008801 · Cited by 30 · see citing works
Epigenetic preparation of future gene induction kinetics
Xiong, J., & Zhu, B. (2025) · Annual Review of Genetics · doi:10.1146/annurev-genet-012825-093148 · Cited by 12 · see citing works
- Authors
- Mayran, A., Khetchoumian, K., Hariri, F., Pastinen, T., Gauthier, Y., Balsalobre, A., & Drouin, J.
- Affiliations
- Montreal Clinical Research Institute (CA)
- McGill University and Génome Québec Innovation Centre (CA)
- Corresponding author
- Drouin, Jacques
- Venue
- Nature Genetics
- Published
- 2018-01-22
- Volume
- 50
- Issue
- 2
- Pages
- 259-269
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2783335334
- Cited by
- 171
- References
- 3
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 16 · 2023: 12 · 2022: 27 · 2021: 25 · 2020: 17 · 2019: 23 · 2018: 16
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Pax7, pioneer transcription factors, chromatin remodeling, DNA methylation, epigenetic memory, heterochromatin, cell fate specification, transcription factor dynamics
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Enhancer Elements, Genetic, Genes, Switch, Mice, Inbred C57BL, Organ Specificity, Protein Binding, Mice, Knockout, Gene Expression Regulation, Developmental, Cell Lineage, DNA Methylation, Genomic Instability, Mice, PAX7 Transcription Factor
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