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Dual function of the epithelial specific ets transcription factor, ELF3, in modulating differentiation.
- Source :
-
Oncogene [Oncogene] 2000 Apr 06; Vol. 19 (15), pp. 1941-9. - Publication Year :
- 2000
-
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.
- Subjects :
- Amino Acid Sequence
Carcinoma, Squamous Cell metabolism
Cell Differentiation
Esophageal Neoplasms metabolism
HeLa Cells
Humans
Keratins genetics
Molecular Sequence Data
Mutation
Proto-Oncogene Proteins c-ets
Tumor Cells, Cultured
DNA-Binding Proteins
Epithelial Cells physiology
Keratins metabolism
Proto-Oncogene Proteins physiology
Transcription Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 19
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 10773884
- Full Text :
- https://doi.org/10.1038/sj.onc.1203441