ArticleNature communications2021
Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- FOXA2 in islet biology: Orchestrating pancreatic development and glucose homeostasis.Genes & diseases · 2026Review
- HNF4α controls growth, identity, and KRAS inhibitor response in invasive mucinous adenocarcinoma of the lung.The Journal of clinical investigation · 2026Article
- Spatiotemporal Profiling Defines the Epithelial and Mesenchymal Transition Window in Embryonic Lung Morphogenesis.Journal of developmental biology · 2026Article
- Histone H4 acetyl-methyllysine marks accessible chromatin that resists compaction.bioRxiv : the preprint server for biology · 2026Article
- The FOXA transcription factors in allergic airway disease and asthma.Frontiers in allergy · 2026Review
- Global DNA methylation signatures associated with chemoresistance and poor prognosis of high grade serous ovarian cancer.Scientific reports · 2025Article
- STAT3 sustains tumorigenicity following mutant KRAS ablation.EMBO reports · 2025Article
- Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids.Developmental cell · 2025Article
- Enhancer regulation in cancer: from epigenetics to mArchives of pharmacal research · 2025Review
- NKX2-1 drives neuroendocrine transdifferentiation of prostate cancer via epigenetic and 3D chromatin remodeling.Nature genetics · 2025Article
- The key regulation of LncRNA MALAT during reprogramming of primary mouse hepatocytes into insulin producing cells.Scientific reports · 2025Article
- PPDPF is not a key regulator of human pancreas development.PLoS genetics · 2025Article
- A noncoding variant confers pancreatic differentiation defect and contributes to diabetes susceptibility by recruiting RXRA.Nature communications · 2024Article
- Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs.Scientific reports · 2024Article
- Systematic dissection of sequence features affecting binding specificity of a pioneer factor reveals binding synergy between FOXA1 and AP-1.Molecular cell · 2024Article
- Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or its regulatory elements.European journal of human genetics : EJHG · 2024Article
- The molecular and cellular choreography of early mammalian lung development.Medical review (2021) · 2024Review
- FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer.Cell death discovery · 2024Review
- Integrative analysis of transcriptomic and epigenomic data reveals distinct patterns for developmental and housekeeping gene regulation.BMC biology · 2024Article
- Pioneer and PRDM transcription factors coordinate bivalent epigenetic states to safeguard cell fate.Molecular cell · 2024Article
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Authors and funding
15 authors.
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Abstract
FOXA pioneer transcription factors (TFs) associate with primed enhancers in endodermal organ precursors. Using a human stem cell model of pancreas differentiation, we here discover that only a subset of pancreatic enhancers is FOXA-primed, whereas the majority is unprimed and engages FOXA upon lineage induction. Primed enhancers are enriched for signal-dependent TF motifs and harbor abundant and strong FOXA motifs. Unprimed enhancers harbor fewer, more degenerate FOXA motifs, and FOXA recruitment to unprimed but not primed enhancers requires pancreatic TFs. Strengthening FOXA motifs at an unprimed enhancer near NKX6.1 renders FOXA recruitment pancreatic TF-independent, induces priming, and broadens the NKX6.1 expression domain. We make analogous observations about FOXA binding during hepatic and lung development. Our findings suggest a dual role for FOXA in endodermal organ development: first, FOXA facilitates signal-dependent lineage initiation via enhancer priming, and second, FOXA enforces organ cell type-specific gene expression via indirect recruitment by lineage-specific TFs.
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