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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 tumor suppressor p53 binding motifs
Gabriele Baniulyte1, Sawyer M Hicks1, Morgan A Sammons1
1Department of Biological Sciences and The RNA Institute, University at Albany, State University of New York, Albany, NY 12222.
Abstract:
The tumor suppressor gene TP53 encodes the DNA binding transcription factor p53 and is one of the most commonly mutated genes in human cancer. Tumor 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.
Insights
This study introduces a database detailing p53 binding sites, integrating DNA and chromatin data. It aids researchers in exploring the tumor suppressor
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- The TP53 gene is a crucial tumor suppressor, frequently mutated in human cancers.
- p53's tumor suppressor function relies on binding DNA and activating target genes.
- Understanding p53's genomic interactions remains a challenge.
Purpose of the Study:
- To present a comprehensive database of p53 binding sites.
- To facilitate hypothesis generation and testing regarding p53's genome-wide activity.
- To integrate diverse genomic and epigenomic data for p53 research.
Main Methods:
- Compilation of DNA and chromatin-based information for putative p53 binding sites.
- Development of a queryable database including experimental p53 binding data.
- Integration of regulatory element activity, genetic variation, conservation, and chromatin features.
Main Results:
- A database enabling queries based on multiple genomic and epigenomic factors.
- Demonstration of use cases for generating novel hypotheses on p53 binding.
- Identification of potential chromatin-based determinants and cell type-specific p53 activity.
Conclusions:
- The database provides a valuable resource for investigating p53's role in cancer.
- Facilitates deeper understanding of p53's transcriptional regulatory logic.
- Supports diverse analyses from local data exploration to web application use.
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