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c-MYC repression of promoter activity through core promoter elements
J M Lucas1, N M Wilkie, J C Lang
1Department of Hematology and Oncology, Ohio State University Hospital, Columbus.
Biochemical and Biophysical Research Communications
|August 16, 1993
Summary
The c-MYC protein was observed to repress its own gene expression. This repression is mediated by cis-acting elements located within the core promoter region of the c-myc gene.
Area of Science:
- Molecular Biology
- Gene Regulation
Background:
- The c-MYC proto-oncogene plays a critical role in cell proliferation, differentiation, and apoptosis.
- Understanding the regulatory mechanisms of c-MYC expression is crucial for comprehending its role in cancer development.
Purpose of the Study:
- To investigate the regulatory elements responsible for c-MYC-mediated repression of the c-myc gene.
- To identify the specific promoter regions involved in this auto-regulatory feedback loop.
Main Methods:
- Transient transfection assays were employed to study gene expression.
- Deletion constructs of the c-myc promoter were analyzed.
- Reporter gene assays were used to quantify promoter activity.
- Site-directed mutagenesis, including TATA box and initiator element replacement, was performed.
Main Results:
- c-MYC was demonstrated to repress the expression of the c-myc promoter.
- Deletion analysis revealed shared cis-acting elements in both P1 and P2 promoters.
- Localization of these cis-acting elements to the core promoter was achieved through functional analysis.
Conclusions:
- The c-myc gene exhibits auto-repression, where the c-MYC protein inhibits its own transcription.
- Specific cis-acting elements within the core promoter are essential for mediating this negative feedback loop.