Transactivation of lung lysozyme expression by Ets family member ESE-1

• Published in: American journal of physiology. Lung cellular and molecular physiology 2007-11, Vol.293 (5), p.L1359-L1368
• Main Authors: Lei, Wanli, Jaramillo, Richard J, Harrod, Kevin S
• Format: Article
• Language: English
• Subjects: Binding sites; Cells; Cells, Cultured; Chromatin Immunoprecipitation; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Electrophoretic Mobility Shift Assay; Enzymes; Epithelium - metabolism; Gene expression; Humans; Lung - cytology; Lung - metabolism; Lungs; Muramidase - genetics; Muramidase - metabolism; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-ets; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA Interference; RNA, Messenger; Tissues; Transcription Factors - antagonists & inhibitors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Transcriptional Activation
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00130.2007

Infectious Diseases Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico Submitted 2 April 2007 ; accepted in final form 23 September 2007 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 transactivated LYZ promoter in reporter gene assays, whereas only ESE-1b dramatically upregulated transcription of endogenous LYZ in both nonpulmonary and pulmonary epithelial cells. Importantly, ESE-1a and ESE-1b could transactivate the LYZ promoter in cultured primary airway epithelial cells. ESE-2 and ESE-3 isoforms were unable to substantially transactivate the lysozyme promoter or upregulate transcription of endogenous LYZ . Two functional consensus Ets sites located in the proximal 130-bp LYZ promoter 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 decreased LYZ transcription. Furthermore, ESE-1 antibody specifically enriched the 130-bp proximal LYZ promoter 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. airway epithelia; Ets proteins; transcriptional regulation; mucosal innate defense Address for reprint requests and other correspondence: K. S. Harrod, Infectious Disease Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108 (e-mail: kharrod{at}lrri.org )