Dissecting the DNA binding landscape and gene regulatory network of p63 and p53

Konstantin Riege, Helene Kretzmer, Arne Sahm, Simon S. McDade, Steve Hoffmann, Martin Fischer

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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.

Original languageEnglish
Article numbere63266
Number of pages26
JournaleLife
Volume9
Early online date02 Dec 2020
DOIs
Publication statusPublished - 14 Dec 2020

Bibliographical note

Publisher Copyright:
© 2020, Riege et al.

Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine

Keywords

  • chromosomes
  • DNA binding landscape
  • gene expression
  • gene regulatory network
  • genetics
  • genomics
  • human
  • p53
  • p63
  • resource
  • squamous cell carcinoma

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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