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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53motifDB: integration of genomic information and tumour suppressor p53 binding motifs
Gabriele Baniulyte1, Sawyer M Hicks1, Morgan A Sammons1
1Department of Biological Sciences and the RNA Institute, University at Albany, SUNY, 1400 Washington Ave, Life Sciences Building Room 2078, Albany, NY 12222, United States.
Abstract:
The tumour suppressor gene TP53 encodes the DNA binding transcription factor p53 and is one of the most mutated genes in human cancer. Tumour suppressor activity requires binding of p53 to its DNA response elements and subsequent transcriptional activation of a diverse set of target genes. Despite decades of close study, the logic underlying p53 interactions with its numerous potential genomic binding sites and target genes is not yet fully understood. Here, we present a database of DNA and chromatin-based information focused on putative p53 binding sites in the human genome to allow users to generate and test new hypotheses related to p53 activity in the genome. Users can query genomic locations based on experimentally observed p53 binding, regulatory element activity, genetic variation, evolutionary conservation, chromatin modification state, and chromatin structure. We present multiple use cases demonstrating the utility of this database for generating novel biological hypotheses, such as chromatin-based determinants of p53 binding and potential cell type-specific p53 activity. All database information is also available as a precompiled SQLite database for use in local analysis or as a Shiny web application. Database URL: https://p53motifDB.its.albany.edu.
Insights
The TP53 tumor suppressor gene
Area of Science:
- Genomics
- Cancer Biology
- Molecular Biology
Background:
- The TP53 gene, encoding the p53 transcription factor, is crucial for tumor suppression.
- p53 activity relies on binding DNA response elements to activate target genes.
- Understanding p53's genomic interactions remains incomplete.
Purpose of the Study:
- To present a comprehensive database of DNA and chromatin information for putative p53 binding sites.
- To enable hypothesis generation and testing regarding p53's genome-wide activity.
- To provide a resource for exploring p53's regulatory logic.
Main Methods:
- Compilation of DNA and chromatin-based data for human p53 binding sites.
- Development of a queryable database integrating multiple data types.
- Creation of a SQLite database and Shiny web application for accessibility.
Main Results:
- The database allows querying p53 binding sites by various genomic features.
- Demonstrated utility in generating hypotheses on chromatin influence and cell-type specificity.
- Provided a centralized resource for p53-centric genomic research.
Conclusions:
- The p53 motif database facilitates novel hypothesis generation in cancer genomics.
- It offers insights into the determinants of p53 binding and activity.
- The resource supports further research into TP53's role in human cancer.
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