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

Mol Cell. 2004 Nov 19;16(4):521-35. doi: 10.1016/j.molcel.2004.10.024.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activating Transcription Factor 2
  • Anthracenes / pharmacology
  • Antineoplastic Agents / toxicity
  • Blotting, Western
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Cisplatin / toxicity
  • Cyclic AMP Response Element-Binding Protein / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA Repair
  • DNA-Binding Proteins / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Small Interfering / metabolism
  • Time Factors
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation*


  • ATF2 protein, human
  • Activating Transcription Factor 2
  • Anthracenes
  • Antineoplastic Agents
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-jun
  • RNA, Small Interfering
  • Transcription Factors
  • pyrazolanthrone
  • Cisplatin