Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/49980
Title: Ets homologous factor (EHF) has critical roles in epithelial dysfunction in airway disease
Authors: Fossum, Sara L.
Mutolo, Michael J.
Tugores, Antonio 
Ghosh, Sujana
Randell, Scott H.
Jones, Lisa C.
Leir, Shih Hsing
Harris, Ann
UNESCO Clasification: 32 Ciencias médicas
2302 Bioquímica
Keywords: ChIP sequencing (ChIP-seq)
ETS transcription factor family
Ets homologous factor (EHF)
Epithelium
Lung injury, et al
Issue Date: 2017
Journal: Journal of Biological Chemistry 
Abstract: The airway epithelium forms a barrier between the internal and external environments. Epithelial dysfunction is critical in the pathology of many respiratory diseases, including cystic fibrosis. Ets homologous factor (EHF) is a key member of the transcription factor network that regulates gene expression in the airway epithelium in response to endogenous and exogenous stimuli. EHF, which has altered expression in inflammatory states, maps to the 5' end of an intergenic region on Chr11p13 that is implicated as a modifier of cystic fibrosis airway disease. Here we determine the functions of EHF in primary human bronchial epithelial (HBE) cells and relevant airway cell lines. Using EHF ChIP followed by deep sequencing (ChIP-seq) and RNA sequencing after EHF depletion, we show that EHF targets in HBE cells are enriched for genes involved in inflammation and wound repair. Furthermore, changes in gene expression impact cell phenotype because EHF depletion alters epithelial secretion of a neutrophil chemokine and slows wound closure in HBE cells. EHF activates expression of the SAM pointed domain-containing ETS transcription factor, which contributes to goblet cell hyperplasia. Our data reveal a critical role for EHF in regulating epithelial function in lung disease.
URI: http://hdl.handle.net/10553/49980
ISSN: 0021-9258
DOI: 10.1074/jbc.M117.775304
Source: Journal of Biological Chemistry[ISSN 0021-9258],v. 292, p. 10938-10949 (Junio 2017)
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