Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress
Articles > Article ยท 2004
Authors: J HAYAKAWA, S MITTAL, Y WANG, Kemal Sami KORKMAZ, E ADAMSON, C ENGLISH, M OMICHI, M MCCLELLAND, D MERCOLA
MOLECULAR CELL, Journal Indexed in SCI Expanded, International, 2004, vol 16, pp 521-535
DOI: 10.1016/j.molcel.2004.10.024
Summary
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.