ARTICLE

Cell Research, 15(6):423-429, June 2005

Epithelium-specific ets transcription factor 2 upregulates cytokeratin 18 expression in pulmonary epithelial cells through an interaction with cytokeratin 18 intron 1

Deanna YANIW^1,2, Jim HU^1,2,3,4,*

¹Programme in Lung Biology Research and the Canadian Institutes of Health Research Group in Lung Development, Hospital for Sick Children, Toronto, Canada M5G 1X8.
² Institute of Medical Science, University of Toronto, Toronto, Canada M5S 1A1.
³ Departments of Paediatrics, University of Toronto, Toronto, Canada M5S 1A1.
⁴ Laboratory Medicine and Pathbiology, University of Toronto, Toronto, Canada M5S 1A1.

Received, Mar 1, 2005 Revised, Apr 5, 2005 Accepted, Apr 16, 2005

Correspondence: Jim HU 01-416-813-6412 (phone) 01-416-813-5771 (fax) jhu@sickkids.on.ca

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The role of Ese-2, an Ets family transcription factor, in gene regulation is not known. In this study, the interaction between Ese-2 and cytokeratin 18 (K18) intron 1 was characterized in lung epithelial cells. Reporter gene assays showed Ese-2 was able to upregulate K18 intron 1 enhanced reporter gene expression by approximately 2-fold. We found that full length Ese-2 did not bind DNA strongly, therefore truncated versions of the protein, containing the ETS domain or Pointed domain, were created and tested in electrophoresis mobility shift assays. Multiple interactions between the ETS domain and putative DNA binding sites within K18 intron 1 were observed, which led to the determination of a possible Ese-2 DNA binding consensus sequence. These experiments suggest that Ese-2 could play a role in the regulation of K18 expression in lung epithelial cells.

Keywords: transcription factor, epithelial cells, cytokeratin 18, airway, gene regulation.