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Ets homologous factor has critical roles in epithelial dysfunction in airway disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE85403 | GEO | 2017/05/22

SECONDARY ACCESSION(S): PRJNA338326

REPOSITORIES: GEO

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Ets homologous factor (EHF) has critical roles in epithelial dysfunction in airway disease.

Project description: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.

| S-EPMC5491778 | biostudies-literature

Ets homologous factor has critical roles in epithelial dysfunction in airway disease [ChIP-seq]

2017-05-22 | GSE85401 | GEO

Ets homologous factor has critical roles in epithelial dysfunction in airway disease [RNA-seq]

2017-05-22 | GSE85402 | GEO

Ets homologous factor has critical roles in epithelial dysfunction in airway disease

Project description:Ets homologous factor has critical roles in epithelial dysfunction in airway disease

| PRJNA338326 | ENA

Ets homologous factor regulates pathways controlling response to injury in airway epithelial cells.

Project description: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.

| S-EPMC4267623 | biostudies-literature

Ets homologous factor regulates pathways controlling response to injury in Calu-3 airway epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-12-23 | E-GEOD-63400 | biostudies-arrayexpress

Ets homologous factor regulates pathways controlling response to injury in Calu-3 airway epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-12-23 | GSE63400 | GEO

Ets homologous factor regulates pathways controlling response to injury in Calu-3 airway epithelial cells [RNA-seq]

2014-12-23 | E-GEOD-63397 | biostudies-arrayexpress

Ets homologous factor regulates pathways controlling response to injury in Calu-3 airway epithelial cells [ChIP-seq]

Project description: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. Examination of EHF binding plus two histone modifications in Calu-3 cells. There are two replicates of the EHF ChIP-seq plus an input sample (control). There is one replicate each of the two histone modifications, plus a second input sample (control).

2014-12-23 | E-GEOD-63398 | biostudies-arrayexpress

Ets homologous factor regulates pathways controlling response to injury in Calu-3 airway epithelial cells [DNAse-seq]

2014-12-23 | E-GEOD-63399 | biostudies-arrayexpress