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Dual function of the epithelial specific ets transcription factor, ELF3, in modulating differentiation

Oncogene volume 19, pages 1941–1949 (2000)Cite this article

Abstract

The ets family of transcription factors comprises many members which contribute to diverse cellular functions that vary depending upon the cell- and tissue-type context. Recently, different groups have identified a novel member of the ets family that is epithelial-specific. Variably called ESE-1, ERT, jen, ESX, this gene is designated currently as ELF3. In order to understand transcriptional regulatory mechanisms mediated by ELF3, we investigated its effect on the human keratin 4 gene promoter based upon the role of keratin 4 in early differentiation of the esophageal squamous epithelium. Interestingly, ELF3 suppressed basal keratin 4 promoter activity in both esophageal and cervical epithelial cancer cell lines, a novel result, while simultaneously activating the late-differentiation linked SPRR2A promoter. Furthermore, serial deletion constructs of the keratin 4 promoter continued to be suppressed by ELF3, a phenomenon that was only partially rescued by ELF3 ets domain mutants, but completely abrogated by deletion of the ELF3 pointed domain. These results suggest that ELF3 may have dual functions in the transcriptional regulation of genes involved in squamous epithelial differentiation. One of these functions may not be exclusively mediated through DNA binding in the context of transcriptional suppression of the keratin 4 promoter.

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Acknowledgements

This work is supported by R01-DK53377 (AK Rustgi), P01-DE12467 (AK Rustgi), The Leonard and Madlyn Abramson Family Cancer Research Institute at the University of Pennsylvania Cancer Center (AK Rustgi), Deutsche Forschungs Gemeinschaft Br 1806/1-1 (FH Brembeck), Deutsche Krebshilfe D/96/17197 (OG Opitz), and the NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases P30 DK50306.

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Authors and Affiliations

  1. Gastroenterology Division, University of Pennsylvania, Philadelphia, 19014, Pennsylvania, PA, USA

    Felix H Brembeck, Oliver G Opitz & Anil K Rustgi

  2. Cancer Center, University of Pennsylvania, Philadelphia, 19014, Pennsylvania, PA, USA

    Anil K Rustgi

  3. Department of Genetics, University of Pennsylvania, Philadelphia, 19014, Pennsylvania, PA, USA

    Anil K Rustgi

  4. Department of Medicine, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, Massachusetts, MA, USA

    Towia A Libermann

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  1. Felix H Brembeck
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Brembeck, F., Opitz, O., Libermann, T. et al. Dual function of the epithelial specific ets transcription factor, ELF3, in modulating differentiation. Oncogene 19, 1941–1949 (2000). https://doi.org/10.1038/sj.onc.1203441

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