ArticleAmerican journal of physiology. Lung cellular and molecular physiology2020
The FOXA1 transcriptional network coordinates key functions of primary human airway epithelial cells.
Article in American journal of physiology. Lung cellular and molecular physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Functional Dissection of TP63 Dual-Promoter Regulatory Elements Reveals Context-Dependent Responsiveness to FOXA2, NKX2-1, SOX9, and TP63-Related Inputs.Current issues in molecular biology · 2026Article
- Pulmonary inflammation in severe pneumonia is characterised by compartmentalised and mechanistically distinct sub-phenotypes.Nature communications · 2026Article
- ceQTL: a co-expression QTL model to detect a variant that affects transcription factor binding and its target regulation.Briefings in bioinformatics · 2026Article
- Epigenetic Dysregulation of the NKX2-1/SPDEF Axis Drives Persistent Goblet Cell Differentiation and Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease.Respirology (Carlton, Vic.) · 2026Article
- The FOXA transcription factors in allergic airway disease and asthma.Frontiers in allergy · 2026Review
- Identification of functional non-coding variants associated with orofacial cleft.Nature communications · 2025Article
- Temporal Transcriptomic Analysis of Periodontal Disease Progression and Its Molecular Links to Systemic Diseases.International journal of molecular sciences · 2025Article
- The Tmem16a chloride channel is required for mucin maturation after secretion from goblet-like cells in the Xenopus tropicalis tadpole skin.Scientific reports · 2024Article
- Article
- Exploring intrinsic variability between cultured nasal and bronchial epithelia in cystic fibrosis.Scientific reports · 2023Article
- Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma.Nucleic acids research · 2023Article
- The use of bioinformatics methods to identify the effects of SARS-CoV-2 and influenza viruses on the regulation of gene expression in patients.Frontiers in immunology · 2023Article
- Early developmental phenotypes in the cystic fibrosis sheep model.FASEB bioAdvances · 2023Article
- A Maverick Review of Common Stem/Progenitor Markers in Lung Development.Stem cell reviews and reports · 2022Review
- Identification of Heme Oxygenase-1 as a Putative DNA-Binding Protein.Antioxidants (Basel, Switzerland) · 2022Article
- FOXA1 prevents nutrients deprivation induced autophagic cell death through inducing loss of imprinting of IGF2 in lung adenocarcinoma.Cell death & disease · 2022Article
- FoxA1 and FoxA2 control growth and cellular identity in NKX2-1-positive lung adenocarcinoma.Developmental cell · 2022Article
- Club cells employ regeneration mechanisms during lung tumorigenesis.Nature communications · 2022Article
- PGC1α Cooperates with FOXA1 to Regulate Epithelial Mesenchymal Transition through the TCF4-TWIST1.International journal of molecular sciences · 2022Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The differentiated functions of the human airway epithelium are coordinated by a complex network of transcription factors. These include the pioneer factors Forkhead box A1 and A2 (FOXA1 and FOXA2), which are well studied in several tissues, but their role in airway epithelial cells is poorly characterized. Here, we define the cistrome of FOXA1 and FOXA2 in primary human bronchial epithelial (HBE) cells by chromatin immunoprecipitation with deep-sequencing (ChIP-seq). Next, siRNA-mediated depletion of each factor is used to investigate their transcriptome by RNA-seq. We found that, as predicted from their DNA-binding motifs, genome-wide occupancy of the two factors showed substantial overlap; however, their global impact on gene expression differed. FOXA1 is an abundant transcript in HBE cells, while FOXA2 is expressed at low levels, and both these factors likely exhibit autoregulation and cross-regulation. FOXA1 regulated loci are involved in cell adhesion and the maintenance of epithelial cell identity, particularly through repression of genes associated with epithelial to mesenchymal transition (EMT). FOXA1 also directly targets other transcription factors with a known role in the airway epithelium such as SAM-pointed domain-containing Ets-like factor (SPDEF). The intersection of the cistrome and transcriptome for FOXA1 revealed enrichment of genes involved in epithelial development and tissue morphogenesis. Moreover, depletion of FOXA1 was shown to reduce the transepithelial resistance of HBE cells, confirming the role of this factor in maintaining epithelial barrier integrity.
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