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A central role for a single c-Myb binding site in a thymic locus control region
K C Ess1, T L Whitaker, G J Cost
1Department of Pediatrics, Children's Hospital Medical Center, University of Cincinnati, Ohio 45229, USA.
Molecular and Cellular Biology
|October 1, 1995
Summary
The c-Myb transcription factor organizes thymocyte-specific gene expression. A single c-Myb binding site within the adenosine deaminase (ADA) gene locus control region (LCR) is critical for its function.
Area of Science:
- Molecular Biology
- Genetics
- Immunology
Background:
- Locus control regions (LCRs) regulate cell-type-specific gene expression.
- The human adenosine deaminase (ADA) gene LCR controls thymocyte expression via an enhancer domain.
Purpose of the Study:
- To identify the critical cis elements and trans-acting factors within the ADA gene LCR enhancer.
- To elucidate the role of c-Myb in regulating ADA gene expression in thymocytes.
Main Methods:
- Reporter gene assays in transiently transfected human cells and stable yeast chromatin.
- Analysis of c-Myb protein localization and expression in T lymphoblasts.
- In vivo assessment of LCR activity in transgenic mice.
Main Results:
- A single c-Myb binding site within the ADA enhancer core is essential for its activity.
- c-Myb protein is present in T lymphoblasts and co-localizes with ADA gene expression.
- Mutation of the c-Myb site significantly reduces enhancer and LCR activity.
Conclusions:
- c-Myb acts as a key organizer of thymocyte-specific ADA gene expression.
- A single binding site for c-Myb within the LCR is sufficient to direct cell-type-specific gene regulation.
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