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A zinc finger homeodomain transcription factor binds specific thyroid hormone response elements
1Department of Biological and Biophysical Sciences, University of Louisville, School of Dentistry, Kentucky 40292, USA. dsdar101@homer.louisville.edu
Molecular and Cellular Endocrinology
|August 15, 1998
Summary
Researchers identified Zinc Finger Homeodomain Enhancer-Binding Protein (Zfhep), a novel transcription factor that binds thyroid hormone response elements (TREs). Zfhep binding is crucial for thyroid hormone receptor regulation of specific gene expression.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Thyroid hormone receptors (TRs) regulate gene expression through thyroid hormone response elements (TREs).
- TRE sequences exhibit significant variability, suggesting the involvement of other factors in TR-mediated gene regulation.
Purpose of the Study:
- To identify transcription factors that bind to the rat glycoprotein hormone alpha-subunit TRE (alpha-sub).
- To characterize the DNA-binding properties and TRE specificity of the identified factor.
Main Methods:
- Screening for transcription factors binding to the alpha-sub TRE.
- cDNA isolation and sequencing to identify the novel protein, Zfhep.
- DNA-binding assays and methylation interference footprinting to determine Zfhep binding sites and specificity.
Main Results:
- A novel cDNA, Zfhep, encoding two zinc finger domains (ZD1, ZD2) and a homeodomain-like region, was isolated.
- Zfhep's zinc finger domains (ZD1/ZD2) bind to TREs of the alpha-subunit, rat growth hormone, and TSHbeta genes.
- Zfhep binds overlapping or adjacent to TR-binding sites on these TREs, indicating sequence dependence beyond the core TR-binding halfsite.
Conclusions:
- Zfhep is a novel transcription factor that interacts with specific TREs, influencing thyroid hormone receptor activity.
- Non-receptor transcription factors like Zfhep play a significant role in modulating gene-specific thyroid hormone regulation.