Parallel profiling of the transcriptome, cistrome, and epigenome in the cellular response to ionizing radiation

Sharon Rashi-Elkeles, Hans Jörg Warnatz, Ran Elkon, Ana Kupershtein, Yuliya Chobod, Arnon Paz, Vyacheslav Amstislavskiy, Marc Sultan, Hershel Safer, Wilfried Nietfeld, Hans Lehrach, Ron Shamir, Marie Laure Yaspo, Yosef Shiloh*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations


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.

Original languageEnglish
Article numberrs3
JournalScience Signaling
Issue number325
StatePublished - 13 May 2014


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