1. Dissecting the DNA binding landscape and gene regulatory network of p63 and p53.
- Author
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Riege K, Kretzmer H, Sahm A, McDade SS, Hoffmann S, and Fischer M
- Subjects
- Binding Sites, Biomarkers, Tumor metabolism, Computational Biology, DNA genetics, Databases, Genetic, Gene Expression Regulation, Head and Neck Neoplasms genetics, Head and Neck Neoplasms metabolism, Head and Neck Neoplasms mortality, Humans, Prognosis, Protein Binding, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck metabolism, Squamous Cell Carcinoma of Head and Neck mortality, Transcription Factors metabolism, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Proteins metabolism, Biomarkers, Tumor genetics, DNA metabolism, Gene Regulatory Networks, Transcription Factors genetics, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Proteins genetics
- Abstract
The transcription factor p53 is the best-known tumor suppressor, but its sibling p63 is a master regulator of epidermis development and a key oncogenic driver in squamous cell carcinomas (SCC). Despite multiple gene expression studies becoming available, the limited overlap of reported p63-dependent genes has made it difficult to decipher the p63 gene regulatory network. Particularly, analyses of p63 response elements differed substantially among the studies. To address this intricate data situation, we provide an integrated resource that enables assessing the p63-dependent regulation of any human gene of interest. We use a novel iterative de novo motif search approach in conjunction with extensive ChIP-seq data to achieve a precise global distinction between p53-and p63-binding sites, recognition motifs, and potential co-factors. We integrate these data with enhancer:gene associations to predict p63 target genes and identify those that are commonly de-regulated in SCC representing candidates for prognosis and therapeutic interventions., Competing Interests: KR, HK, AS, SM, SH, MF No competing interests declared, (© 2020, Riege et al.)
- Published
- 2020
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