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

doi:10.1016/j.celrep.2014.06.030

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 journal › Article › peer-review

49 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 language	English (US)
Pages (from-to)	514-527
Number of pages	14
Journal	Cell Reports
Volume	8
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2014.06.030
State	Published - Jul 24 2014
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2014.06.030

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@article{662a7aa0238b4bce94f92765f6f4bb15,

title = "A Comprehensive and High-Resolution Genome-wide Response of p53 to Stress",

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.",

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

note = "Funding Information: We thank Joachin Espinosa for compiled lists of p53 target genes and for comments on the manuscript. This work was supported by NIH grants DK065806 (to R.C.H.), CA136856 (to Y.W.), and ES013768 (to B.F.P.). B.F.P. has a financial interest in Peconic, LLC, which utilizes the ChIP-exo technology implemented in this study and could potentially benefit from the outcomes of this research. ",

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doi = "10.1016/j.celrep.2014.06.030",

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AU - Chang, Gue Su

AU - Chen, Xiangyun Amy

AU - Park, Bongsoo

AU - Rhee, Ho Sung

AU - Li, Pingxin

AU - Han, Kang Hoo

AU - Mishra, Tejaswini

AU - Chan-Salis, Ka Yim

AU - Li, Yunfei

AU - Hardison, Ross C.

AU - Wang, Yanming

AU - Pugh, B. Franklin

N1 - Funding Information: We thank Joachin Espinosa for compiled lists of p53 target genes and for comments on the manuscript. This work was supported by NIH grants DK065806 (to R.C.H.), CA136856 (to Y.W.), and ES013768 (to B.F.P.). B.F.P. has a financial interest in Peconic, LLC, which utilizes the ChIP-exo technology implemented in this study and could potentially benefit from the outcomes of this research.

PY - 2014/7/24

Y1 - 2014/7/24

N2 - 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.

AB - 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.

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

Abstract

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