Transactivation of lung lysozyme expression by Ets family member ESE-1.
Transactivation of lung lysozyme expression by Ets family member ESE-1.
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Ets 家族成员 ESE-1 对肺溶菌酶表达的反式激活。
DOI：
10.1152/ajplung.00130.2007
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Harrod,KevinS
中科院分区：
文献类型：
--
作者：
Lei,Wanli;Jaramillo,RichardJ;Harrod,KevinS
Epithelial-specific Ets (ESE) transcription factors, consisting of ESE-1, ESE-2, and ESE-3, are constitutively expressed in distinct epithelia of mucosal tissues, including the lung. Each ESE member exhibits alternative splicing and yields at least two isoforms (a and b) with transcriptional targets largely unidentified. The studies described herein define a novel role for ESE transcription factors in transactivation of the human lysozyme gene (LYZ), an essential component of innate defense in lung epithelia. Of the six ESE isoforms, ESE-1a and ESE-1b transactivatedLYZpromoter in reporter gene assays, whereas only ESE-1b dramatically upregulated transcription of endogenousLYZin both nonpulmonary and pulmonary epithelial cells. Importantly, ESE-1a and ESE-1b could transactivate theLYZpromoter in cultured primary airway epithelial cells. ESE-2 and ESE-3 isoforms were unable to substantially transactivate the lysozyme promoter or upregulate transcription of endogenousLYZ. Two functional consensus Ets sites located in the proximal 130-bpLYZpromoter were responsive to ESE-1b as identified by site-directed mutagenesis and DNA binding assays. Short hairpin RNA attenuation of endogenous ESE-1b mRNA levels in lung epithelia resulted in decreasedLYZtranscription. Furthermore, ESE-1 antibody specifically enriched the 130-bp proximalLYZpromoter in chromatin immunoprecipitation analyses. These findings define a novel role for ESE transcription factors in regulating lung innate defense and suggest distinct regulatory functions for ESE family members.
