Epithelium-specific ets transcription factor 2 upregulates cytokeratin 18 expression in pulmonary epithelial cells through an interaction with cytokeratin 18 intron 1.
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.
Programme in Lung Biology Research and the Canadian Institutes of Health Research Group in Lung Development, Hospital for Sick Children, Toronto, Canada M5G 1X8.
Deanna
D
Yaniw
Jim
J
Hu
D001483:Base Sequence; D001665:Binding Sites / Q000502:physiology; D002460:Cell Line; D016384:Consensus Sequence; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns / Q000502:physiology*; D007633:Keratins / Q000096:biosynthesis* / Q000235:genetics*; D008168:Lung; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000502:physiology*; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C116038:ELF5 protein, human; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D007633:Keratins