ELF5 regulates epithelial integrity independently of EHF [RNA-seq]

E74-like ETS transcription factor 5 (ELF5) is one of three epithelial ETS family transcription factors. The ELF5 gene maps to chr11p13 where it is located adjacent to another epithelial ETS factor gene, ETS homologous factor (EHF). This genomic interval is associated with lung disease. The functions of ELF5 in the airway epithelium are not well studied, in large part due to a lack of cellular models expressing the gene. Using scRNA-seq data from primary human bronchial (HBE) and nasal (HNE) epithelial cells we show ELF5 expression in subsets of ciliated and secretory cells, implicating a role for this factor in the airway epithelium. Next, we generate cistrome and transcriptome data for ELF5 in another epithelial cell type with abundant ELF5, and use bioinformatic tools to reveal the potential functions of this factor in the airway epithelium. ELF5 has a strong repressive function in epithelial cells, where it has a profound impact on organization of the extracellular matrix. Activation of ELF5 expression in primary HBE cells using CRISPRa enhanced transepithelial resistance (TER) and wound repair. These results illustrate an important role for ELF5 in maintaining airway epithelial integrity, which is critical to lung health. Furthermore, ELF5 can act independently from EHF and exhibits opposite effects in the airway epithelium.