TY - JOUR
T1 - Parallel profiling of the transcriptome, cistrome, and epigenome in the cellular response to ionizing radiation
AU - Rashi-Elkeles, Sharon
AU - Warnatz, Hans Jörg
AU - Elkon, Ran
AU - Kupershtein, Ana
AU - Chobod, Yuliya
AU - Paz, Arnon
AU - Amstislavskiy, Vyacheslav
AU - Sultan, Marc
AU - Safer, Hershel
AU - Nietfeld, Wilfried
AU - Lehrach, Hans
AU - Shamir, Ron
AU - Yaspo, Marie Laure
AU - Shiloh, Yosef
PY - 2014/5/13
Y1 - 2014/5/13
N2 - The DNA damage response (DDR) is a vast signaling network that is robustly activated by DNA double-strand breaks, the critical lesion induced by ionizing radiation (IR). Althoughmuch of this response operates at the protein level, a critical component of the network sustains many DDR branches by modulating the cellular transcriptome. Using deep sequencing, we delineated three layers in the transcriptional response to IR in humanbreast cancer cells: changes in the expression of genes encoding proteins or long noncoding RNAs, alterations in genomic binding by key transcription factors, and dynamics of epigenetic markers of active promoters and enhancers. We identified protein-coding and previously unidentified noncoding genes that were responsive to IR, and demonstrated that IR-induced transcriptional dynamics wasmediated largely by the transcription factors p53 and nuclear factor κB (NF-κB) and was primarily dependent on the kinase ataxia-telangiectasia mutated (ATM). The resultant data set provides a rich resource for understanding a basic, underlying component of a critical cellular stress response.
AB - The DNA damage response (DDR) is a vast signaling network that is robustly activated by DNA double-strand breaks, the critical lesion induced by ionizing radiation (IR). Althoughmuch of this response operates at the protein level, a critical component of the network sustains many DDR branches by modulating the cellular transcriptome. Using deep sequencing, we delineated three layers in the transcriptional response to IR in humanbreast cancer cells: changes in the expression of genes encoding proteins or long noncoding RNAs, alterations in genomic binding by key transcription factors, and dynamics of epigenetic markers of active promoters and enhancers. We identified protein-coding and previously unidentified noncoding genes that were responsive to IR, and demonstrated that IR-induced transcriptional dynamics wasmediated largely by the transcription factors p53 and nuclear factor κB (NF-κB) and was primarily dependent on the kinase ataxia-telangiectasia mutated (ATM). The resultant data set provides a rich resource for understanding a basic, underlying component of a critical cellular stress response.
UR - http://www.scopus.com/inward/record.url?scp=84900552326&partnerID=8YFLogxK
U2 - 10.1126/scisignal.2005032
DO - 10.1126/scisignal.2005032
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AN - SCOPUS:84900552326
SN - 1945-0877
VL - 7
JO - Science Signaling
JF - Science Signaling
IS - 325
M1 - rs3
ER -