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FoxA proteins regulate H19 endoderm enhancer E1 and exhibit developmental changes in enhancer binding in vivo
1Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose St., Lexington, KY 40536-0298, USA.
Molecular and Cellular Biology
|October 16, 2004
Summary
Transcription factor FoxA binds to the H19 E1 enhancer, regulating H19 gene expression during development. This binding is crucial for H19 activation in fetal liver and repression in adult liver.
Area of Science:
- Developmental Biology
- Gene Regulation
- Epigenetics
Background:
- The H19-Igf2 locus has complex regulatory elements controlling its expression.
- Factors binding to these enhancers, particularly the H19 E1 enhancer, remain largely unidentified.
Purpose of the Study:
- To identify factors binding to the H19 E1 enhancer.
- To elucidate the role of identified factors in the developmental and tissue-specific regulation of H19 expression.
Main Methods:
- Chromatin immunoprecipitation (ChIP) to detect protein-DNA interactions.
- Site-directed mutagenesis to assess the functional impact of identified binding sites.
- Analysis of H19 expression and FoxA binding in different cell types and developmental stages.
Main Results:
- Two functional FoxA binding sites were identified in the H19 E1 enhancer.
- FoxA binding to E1 correlates with H19 expression in fetal liver and differentiating F9 cells (VE vs. PE).
- FoxA binding decreases in adult liver despite protein presence, indicating regulated accessibility.
Conclusions:
- FoxA plays a critical role in the developmental activation and postnatal repression of H19 expression.
- This is the first identification of a tissue-specific factor involved in H19's developmental control.
- FoxA protein presence alone is insufficient for binding; accessibility mechanisms are key.