title: Ets homologous factor regulates pathways controlling response to injury in airway epithelial cells.
abstract: Ets homologous factor (EHF) is an Ets family transcription factor expressed in many epithelial cell types including those lining the respiratory system. Disruption of the airway epithelium is central to many lung diseases, and a network of transcription factors coordinates its normal function. EHF can act as a transcriptional activator or a repressor, though its targets in lung epithelial cells are largely uncharacterized. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq), showed that the majority of EHF binding sites in lung epithelial cells are intergenic or intronic and coincide with putative enhancers, marked by specific histone modifications. EHF occupies many genomic sites that are close to genes involved in intercellular and cell-matrix adhesion. RNA-seq after EHF depletion or overexpression showed significant alterations in the expression of genes involved in response to wounding. EHF knockdown also targeted genes in pathways of epithelial development and differentiation and locomotory behavior. These changes in gene expression coincided with alterations in cellular phenotype including slowed wound closure and increased transepithelial resistance. Our data suggest that EHF regulates gene pathways critical for epithelial response to injury, including those involved in maintenance of barrier function, inflammation and efficient wound repair.
authors.affiliation: Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Fossum
authors.affiliation: Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mutolo
authors.affiliation: Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Marsico Lung Institute, University of North Carolina Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Dang
authors.affiliation: Marsico Lung Institute, University of North Carolina Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Wanda K
authors.initials: WK
authors.lastname: O'Neal
authors.affiliation: Marsico Lung Institute, University of North Carolina Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Knowles
authors.affiliation: Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Shih-Hsing
authors.initials: SH
authors.lastname: Leir
authors.affiliation: Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA ann-harris@northwestern.edu.
authors.forename: Ann
authors.initials: A
authors.lastname: Harris
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D058977:Molecular Sequence Annotation; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000502:physiology; D014945:Wound Healing
chemical_list: D050783:Proto-Oncogene Proteins c-ets