Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress |
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Authors: | Hayakawa Jun Mittal Shalu Wang Yipeng Korkmaz Kemal S Adamson Eileen English Christopher Ohmichi Masahide Omichi Masahide McClelland Michael Mercola Dan |
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Institution: | Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, California 92121, USA. |
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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. |
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