Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq

• DOI: 10.1186/s12931-021-01617-y
• Publication Date: 2021-01-21T07:02:57Z
• Authors: Justyna A. Karolak; Tomasz Gambin; Przemyslaw Szafra...; Paweł Stankiewicz
• Keywords: Lung morphogenesis; 0301 basic medicine; RC705-779; Research; Forkhead Transcription Factors; Fetal Development; Diseases of the respiratory system; 03 medical and health sciences; Transcriptional regulation; Chromatin Immunoprecipitation Sequencing; Humans; Hedgehog Proteins; Motif enrichment; T-Box Domain Proteins; Fibroblast Growth Factor 10; Lung; Protein Binding

AbstractBackgroundThe epithelial-mesenchymal signaling involving SHH-FOXF1, TBX4-FGF10, and TBX2 pathways is an essential transcriptional network operating during early lung organogenesis. However, precise regulatory interactions between different genes and proteins in this pathway are incompletely understood.MethodsTo identify TBX2 and TBX4 genome-wide binding sites, we performed chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) in human fetal lung fibroblasts IMR-90.ResultsWe identified 14,322 and 1,862 sites strongly-enriched for binding of TBX2 and TBX4, respectively, 43.95% and 18.79% of which are located in the gene promoter regions. Gene Ontology, pathway enrichment, and DNA binding motif analyses revealed a number of overrepresented cues and transcription factor binding motifs relevant for lung branching that can be transcriptionally regulated by TBX2 and/or TBX4. In addition, TBX2 and TBX4 binding sites were found enriched around and withinFOXF1and its antisense long noncoding RNAFENDRR,indicating that the TBX4-FGF10 cascade may directly interact with the SHH-FOXF1 signaling.ConclusionsWe highlight the complexity of transcriptional network driven by TBX2 and TBX4 and show that disruption of this crosstalk during morphogenesis can play a substantial role in etiology of lung developmental disorders.