title: Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress.
abstract: The NH2-terminal Jun kinases (JNKs) function in diverse roles through phosphorylation and activation of AP-1 components including ATF2 and c-Jun. However, the genes that mediate these processes are poorly understood. A model phenotype characterized by rapid activation of Jun kinase and enhanced DNA repair following cisplatin treatment was examined using chromatin immunoprecipitation with antibodies against ATF2 and c-Jun or their phosphorylated forms and hybridization to promoter arrays. Following genotoxic stress, we identified 269 genes whose promoters are bound upon phosphorylation of ATF2 and c-Jun. Binding did not occur following treatment with transplatin or the JNK inhibitor SP600125 or JNK-specific siRNA. Of 89 known DNA repair genes represented on the array, 23 are specifically activated by cisplatin treatment within 3-6 hr. Thus, the genotoxic stress response occurs at least partly via activation of ATF2 and c-Jun, leading to large-scale coordinate gene expression dominated by genes of DNA repair.
authors.affiliation: Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, California 92121, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Hayakawa
authors.forename: Shalu
authors.initials: S
authors.lastname: Mittal
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Kemal S
authors.initials: KS
authors.lastname: Korkmaz
authors.forename: Eileen
authors.initials: E
authors.lastname: Adamson
authors.forename: Christopher
authors.initials: C
authors.lastname: English
authors.forename: Masahide
authors.initials: M
authors.lastname: Ohmichi
authors.forename: Masahide
authors.initials: M
authors.lastname: Omichi
authors.forename: Michael
authors.initials: M
authors.lastname: McClelland
authors.forename: Dan
authors.initials: D
authors.lastname: Mercola
mesh_terms: D051698:Activating Transcription Factor 2; D000873:Anthracenes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D002945:Cisplatin / Q000633:toxicity; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D000873:Anthracenes; D000970:Antineoplastic Agents; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D014157:Transcription Factors; C432165:pyrazolanthrone; D002945:Cisplatin