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

Ets homologous factor regulates pathways controlling response to injury in airway epithelial cells.
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DOI:
10.1093/nar/gku1146
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发表时间:
2014-12-16
影响因子:
14.9
通讯作者:
Harris A
Harris A
中科院分区:
生物学2区
文献类型:
--
作者:
Fossum SL;Mutolo MJ;Yang R;Dang H;O'Neal WK;Knowles MR;Leir SH;Harris A

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Ets同源因子(EHF)是一个Ets家族转录因子,在许多上皮细胞中表达,包括呼吸系统上皮细胞。气道上皮的破坏是许多肺部疾病的核心,转录因子网络协调其正常功能。EHF可以作为转录激活因子或抑制因子,尽管其在肺上皮细胞中的靶点在很大程度上是未知的。染色质免疫沉淀和深度测序(ChIP-seq)显示,肺上皮细胞中的大多数EHF结合位点是基因间的或内含子的,并且与假定的增强子一致,以特异性组蛋白修饰为标志。EHF占据许多基因组位点,这些位点与参与细胞间和细胞-基质粘附的基因接近。EHF缺失或过表达后的RNA-seq显示,参与损伤反应的基因表达发生了显著变化。EHF基因敲除还针对上皮发育、分化和运动行为通路中的基因。这些基因表达的变化与细胞表型的改变相一致,包括伤口愈合减慢和上皮耐药增加。我们的数据表明,EHF调节了对上皮损伤反应至关重要的基因通路,包括那些参与维持屏障功能、炎症和有效伤口修复的基因通路。
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.
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