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Published on: November 29, 2016
ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target
1New England Baptist Bone and Joint Institute, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
Most cancers originate as a result of aberrant gene expression in mainly glandular epithelial tissues leading to defects in epithelial cell differentiation. The latter is governed by distinct sets of transcriptional regulators. Here we report the characterization of epithelium-specific Ets factor, family member 3 (ESE-3), a novel member of the ESE subfamily of Ets transcription factors. ESE-3 shows highest homology to two other epithelium restricted Ets factors, ESE-1 and ESE-2. ESE-3, like ESE-1 and ESE-2, is exclusively expressed in a subset of epithelial cells with highest expression in glandular epithelium such as prostate, pancreas, salivary gland, and trachea. A potential role in branching morphogenesis is suggested, since ESE-3 transactivates the c-MET promoter via three high affinity binding sites. Additionally, ESE-3 binding to DNA sequences in the promoters of several glandular epithelium-specific genes suggests a role for ESE-3 in later stages of glandular epithelium differentiation. Although ESE-3 and ESE-1 bind with similar affinity to various Ets binding sites, ESE-3 and ESE-1 differ significantly in their ability to transactivate the promoters containing these sites. Our results support the notion that ESE-1, ESE-2, and ESE-3 represent a unique epithelium-specific subfamily of Ets factors that have critical but distinct functions in epithelial cell differentiation and proliferation.
Insights
Researchers identified epithelium-specific Ets factor, family member 3 (ESE-3), a novel transcription factor. ESE-3 plays distinct roles in epithelial cell differentiation and proliferation, particularly in glandular tissues.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Aberrant gene expression in epithelial tissues can lead to cancer.
- Epithelial cell differentiation is regulated by specific transcriptional regulators.
- Ets transcription factors play crucial roles in cellular processes.
Purpose of the Study:
- To characterize a novel epithelium-specific Ets factor, ESE-3.
- To investigate the role of ESE-3 in epithelial cell differentiation and proliferation.
- To compare ESE-3 with related Ets factors (ESE-1, ESE-2).
Main Methods:
- Gene expression analysis to determine ESE-3 tissue distribution.
- Promoter transactivation assays to study ESE-3 function.
- DNA binding assays to assess ESE-3 interaction with gene promoters.
Main Results:
- ESE-3 is exclusively expressed in a subset of epithelial cells, notably glandular epithelium (prostate, pancreas, salivary gland, trachea).
- ESE-3 transactivates the c-MET promoter, suggesting a role in branching morphogenesis.
- ESE-3 binds to promoters of glandular epithelium-specific genes, indicating involvement in differentiation.
- ESE-3 exhibits distinct transactivation capabilities compared to ESE-1, despite similar DNA binding affinity.
Conclusions:
- ESE-3 is a novel member of an epithelium-specific Ets factor subfamily (including ESE-1, ESE-2).
- This subfamily plays critical, yet distinct, roles in epithelial cell differentiation and proliferation.
- ESE-3 likely contributes to glandular epithelial development and function.
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