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Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
Published on: June 28, 2018
Comparative binding of p53 to its promoter and DNA recognition elements
Richard L Weinberg1, Dmitry B Veprintsev, Mark Bycroft
1Cambridge University Chemical Laboratory and MRC Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK.
Journal of Molecular Biology
|April 14, 2005
Summary
The tumor suppressor p53 protein exhibits selective DNA binding, with higher affinity for cell cycle arrest genes than apoptosis genes. This specificity influences p53
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- The p53 protein is a crucial tumor suppressor that acts as a transcription factor.
- p53 regulates genes involved in DNA repair, cell cycle arrest, apoptosis, and its own degradation.
Purpose of the Study:
- To investigate the role of DNA-binding selectivity in p53's transcriptional regulation.
- To quantify the binding affinities of p53 to various recognition elements in vitro.
Main Methods:
- A tetrameric p53 construct (p53CT) was used to measure in vitro binding affinities.
- Binding affinities were assessed for 20 representative p53 recognition elements.
- Results were compared with full-length p53 binding and published cell-based assays.
Main Results:
- p53 binding affinities to different recognition elements varied up to 50-fold and were cooperative.
- High-affinity binding was observed for recognition elements in cell cycle arrest genes and some apoptosis genes.
- Lower-affinity binding sites were predominantly found in apoptosis-related genes.
Conclusions:
- The specificity of p53's DNA-binding interactions is a key factor in regulating its activity.
- Quantitative binding data align with findings from cell-based functional assays.
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