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Out with the old, in with the new: Pioneer transcription factors as activators and repressors of lineage specification genes.
Mol Cell
February 2024
Eukaryotic Transcriptional Regulation Group, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address:
Article Synopsis
- Matsui et al. investigate how pioneer transcription factors influence lineage determination in cells.
- They discover that these factors work alongside PRDM family proteins to regulate cell fate by inhibiting the expression of alternative lineages and premature genes.
- The research highlights the role of bivalent enhancers in maintaining this regulatory balance.
Pioneer and PRDM transcription factors coordinate bivalent epigenetic states to safeguard cell fate.
Mol Cell
February 2024
Division of Developmental Biology, Center for Stem Cell & Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address:
Pioneer transcription factors (TFs) regulate cell fate by establishing transcriptionally primed and active states. However, cell fate control requires the coordination of both lineage-specific gene activation and repression of alternative-lineage programs, a process that is poorly understood. Here, we demonstrate that the pioneer TF FOXA coordinates with PRDM1 TF to recruit nucleosome remodeling and deacetylation (NuRD) complexes and Polycomb repressive complexes (PRCs), which establish highly occupied, accessible nucleosome conformation with bivalent epigenetic states, thereby preventing precocious and alternative-lineage gene expression during human endoderm differentiation.
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