A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress
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 exonucl...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714004999 |
| _version_ | 1828868137178628096 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Gue Su Chang |
| collection | DOAJ |
| description | 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-damage stress-response network. Thus, p53 plays a comprehensive role in regulating the stress-response network, including regulating noncoding transcription. |
| first_indexed | 2024-12-13T05:25:18Z |
| format | Article |
| id | doaj.art-822ae1cebfc84705bbc9f56e64b571d5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T05:25:18Z |
| publishDate | 2014-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-822ae1cebfc84705bbc9f56e64b571d52022-12-21T23:58:13ZengElsevierCell Reports2211-12472014-07-018251452710.1016/j.celrep.2014.06.030A Comprehensive and High-Resolution Genome-wide Response of p53 to StressGue Su Chang0Xiangyun Amy Chen1Bongsoo Park2Ho Sung Rhee3Pingxin Li4Kang Hoo Han5Tejaswini Mishra6Ka Yim Chan-Salis7Yunfei Li8Ross C. Hardison9Yanming Wang10B. Franklin Pugh11Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USACenter for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USATumor 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-damage stress-response network. Thus, p53 plays a comprehensive role in regulating the stress-response network, including regulating noncoding transcription.http://www.sciencedirect.com/science/article/pii/S2211124714004999 |
| spellingShingle | 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 A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress Cell Reports |
| title | A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress |
| title_full | A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress |
| title_fullStr | A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress |
| title_full_unstemmed | A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress |
| title_short | A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress |
| title_sort | comprehensive and high resolution genome wide response of p53 to stress |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714004999 |
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