Pioneer factors are a group of transcription factors with important roles in gene regulation during development. Their unique ability to bind to compacted chromatin, promoting its remodelling for gene expression, sets them apart from other regulatory proteins and makes them essential players in cellular differentiation, fate determination and reprogramming. Here, we have tasked five experts with discussing our current understanding of pioneer factors and their functions to showcase why exploring these proteins offers unique insights into gene regulation and cellular identity.
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Acknowledgements
M.L.B. is supported by US National Institutes of Health (NIH) grant R01HG012246. Research in the laboratory of J.D. is supported by the Canadian Institutes of Health Research (CIHR) and Compute Canada. M.M.H. is funded by NIH R35GM136298 and R01NS111647, and is a Romnes Faculty Fellow and Vilas Faculty Mid-Career Investigator. K.S.Z. is supported by NIH grant R01 GM36477.
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Martha L. Bulyk is a Professor of Medicine and Pathology at Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. Her research laboratory develops high-throughput experimental and computational methods for investigations of transcription factors and cis-regulatory elements, with a focus on mechanisms of their interactions and the impact of genetic variants on gene regulation.
Jacques Drouin is Director of the Laboratory of Molecular Genetics at the Institut de recherches cliniques de Montréal, Canada with academic positions at Université de Montréal and McGill University. His research focuses on transcriptional and epigenetic regulation of pituitary cell differentiation and function. He is a Fellow of the Royal Society of Canada and of the Canadian Academies of Sciences and of Health Sciences.
Melissa M. Harrison is a Professor of Biomolecular Chemistry at the University of Wisconsin School of Medicine and Public Health, USA. Her research is focused on transcriptional control of conserved developmental transitions. One major area of investigation is understanding the rapid and efficient genomic reprogramming that occurs during early development to establish a totipotent embryo. She was a Vallee Scholar and is a Romnes Faculty Fellow and Vilas Faculty Mid-Career Investigator.
Jussi Taipale is a professor at Cambridge University, UK, at Karolinska Institutet, Sweden and at University of Helsinki, Finland. His laboratory focuses on high-throughput biology — combining experimental and computational approaches to understand two systems-level questions that are presently poorly understood: the mechanisms that control growth of tissues and organisms, and the rules that specify how DNA sequence determines when and where genes are expressed.
Kenneth S. Zaret is Professor of Cell and Developmental Biology at the Perelman School of Medicine, University of Pennsylvania, USA. His research focuses on how to overcome chromatin barriers during cell fate changes in embryogenesis, regeneration and disease. Ken is the Director of the Institute for Regenerative Medicine at University of Pennsylvania and originated the concept of pioneer factors.
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Bulyk, M.L., Drouin, J., Harrison, M.M. et al. Pioneer factors — key regulators of chromatin and gene expression. Nat Rev Genet 24, 809–815 (2023). https://doi.org/10.1038/s41576-023-00648-z
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DOI: https://doi.org/10.1038/s41576-023-00648-z
