A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress

Gue Su Chang, Xiangyun Amy Chen, Bongsoo Park, Ho Sung Rhee, Pingxin Li, Kang Hoo Han, Tejaswini Mishra, Ka Yim Chan-Salis, Yunfei Li, Ross C. Hardison, Yanming Wang, B. Franklin Pugh

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Tumor suppressor p53 regulates transcription of stress-response genes. Many p53 targets remain undiscovered because of uncertainty as to where p53 binds in the genome and the fact that few genes reside near p53-bound recognition elements (REs). Using chromatin immunoprecipitation followed by exonuclease treatment (ChIP-exo), we associated p53 with 2,183 unsplit REs. REs were positionally constrained with other REs and other regulatory elements, which may reflect structurally organized p53 interactions. Surprisingly, stress resulted in increased occupancy of transcription factor IIB (TFIIB) and RNA polymerase (Pol) II near REs, which was reduced when p53 was present. A subset associated with antisense RNA near stress-response genes. The combination of high-confidence locations for p53/REs, TFIIB/Pol II, and their changes in response to stress allowed us to identify 151 high-confidence p53-regulated genes, substantially increasing the number of p53 targets. These genes composed a large portion of a predefined DNA-damagestress-response network. Thus, p53 plays a comprehensive role in regulating the stress-response network, including regulating noncoding transcription.

Original languageEnglish (US)
Pages (from-to)514-527
Number of pages14
JournalCell Reports
Volume8
Issue number2
DOIs
StatePublished - Jul 24 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Chang, G. S., Chen, X. A., Park, B., Rhee, H. S., Li, P., Han, K. H., Mishra, T., Chan-Salis, K. Y., Li, Y., Hardison, R. C., Wang, Y., & Pugh, B. F. (2014). A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress. Cell Reports, 8(2), 514-527. https://doi.org/10.1016/j.celrep.2014.06.030