Repression of new p53 targets revealed by ChIP on chip experiments

Cell Cycle. 2006 May;5(10):1102-10. doi: 10.4161/cc.5.10.2777. Epub 2006 May 15.


Following DNA-damage, the tumor suppressor p53 activates G1/S blocking and apoptotic genes, and represses other genes, including those involved in G2/M transition. In this latter system, it acts through the CCAAT-binding histone-like NF-Y. Several groups have reported that p53 is associated to promoters in unstressed conditions. We developed an oligo-based array containing 179 human promoters, enriched in genes involved in the DNA-damage and ER-stress response. We performed ChIP on chip experiments with p53 and NF-Y in cells under normal growing conditions. We identified 46 new p53 targets and noted (i) a significant enrichment in genes of the ER-stress response, including crucial regulators such as XBP1 and C/EBPbeta (ii) genes whose products are involved in the regulation of p53 function. Several genes were validated by conventional ChIP. DNA-damage dependent PCAF-mediated acetylation was observed on most, but not all promoters. The effect of p53 activation was checked by RT-PCR and transfections in HCT116 wt, E6 and p53-/- cells: most promoters were actively repressed upon Adriamycin treatment or following p53 transfection in p53-/- cells. In particular, the behaviour of some of the genes (BRCA1, RAD23 and RAD17) is consistent with a feedback loop regulation on p53 levels. Finally, there is a large overlap (66%) between p53 and NF-Y targets. Our data reinstate the physiological importance of p53 promoter recognition and direct transcriptional repression as a mechanism to cope with DNA-damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • CCAAT-Binding Factor / genetics
  • CCAAT-Binding Factor / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Damage* / genetics
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Doxorubicin
  • Gene Expression Profiling / methods*
  • HCT116 Cells
  • Histone Acetyltransferases
  • Humans
  • Oligonucleotide Array Sequence Analysis*
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Transcription Factors
  • Transcription, Genetic
  • Transfection
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • p300-CBP Transcription Factors


  • Alkylating Agents
  • BRCA1 Protein
  • CCAAT-Binding Factor
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • RNA, Messenger
  • Rad17 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • RAD23A protein, human
  • Doxorubicin
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • DNA Repair Enzymes