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| Status |
Public on Jan 12, 2022 |
| Title |
The FOXA1 transcriptional network coordinates key functions of primary human airway epithelial cells. [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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 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 these factors likely both exhibit auto-regulation and cross-regulation. FOXA1 regulated genes involved in cell adhesion and the maintenance of the 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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| Overall design |
Examination of the transcriptome following siRNA-mediated depletion of FOXA1, FOXA2 or both
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| Contributor(s) |
Paranjapye A, Sabith Ebron J, Mutolo M, Leir S, Harris A |
| Citation(s) |
32432922 |
| |
| Submission date |
Jan 16, 2020 |
| Last update date |
Jan 12, 2022 |
| Contact name |
Ann Harris |
| E-mail(s) |
[email protected]
|
| Organization name |
Case Western Reserve University
|
| Department |
Genetics and Genome Sciences
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| Street address |
2109 Adelbert Rd Building
|
| City |
Cleveland |
| State/province |
Ohio |
| ZIP/Postal code |
44106 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE143769 |
The FOXA1 transcriptional network coordinates key functions of primary human airway epithelial cells. |
|
| Relations |
| BioProject |
PRJNA601641 |
| SRA |
SRP242180 |
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