Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress


HAYAKAWA J., MITTAL S., WANG Y., Korkmaz K. S. , ADAMSON E., ENGLISH C., ...More

MOLECULAR CELL, vol.16, no.4, pp.521-535, 2004 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 16 Issue: 4
  • Publication Date: 2004
  • Doi Number: 10.1016/j.molcel.2004.10.024
  • Title of Journal : MOLECULAR CELL
  • Page Numbers: pp.521-535

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.