Promoter-specific p53-dependent histone acetylation following DNA damage.

Richard Derek Iggo, M. D Kaeser,

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

We have used chromatin immunoprecipitation (ChIP) to measure p53-dependent histone acetylation at the p21, MDM2, and PUMA promoters. The pattern of histone acetylation was different at each promoter. H3 and H4 acetylation increased at both the p21 and PUMA promoters in response to p53 activation, whereas there was only a minimal increase in H4 acetylation and no increase in H3 acetylation at the MDM2 promoter. The high p53 occupancy of the p21, MDM2 and PUMA promoters has been attributed to the presence of two p53 binding sites in these promoters, but mutation of the p53 binding sites in integrated p21 promoter constructs showed that the two sites in the p21 promoter do not cooperate to stabilize p53 binding. Despite 10-fold higher p53 binding to the proximal than the distal site in the p21 promoter, both sites showed similar patterns of H3 and H4 acetylation. Mutation of the binding sites showed that acetylation of the proximal, low-affinity site requires p53 binding to that site but not to the distal, high-affinity site. Since low-affinity p53 binding sites can confer strong acetylation, the DNA binding affinity in vitro is an unreliable guide to the likely importance of p53 in regulating candidate target genes in vivo.

Original languageEnglish
Pages (from-to)4007-4013
Number of pages7
JournalOncogene
Volume23
Issue number22
DOIs
Publication statusPublished - 13 May 2004

Keywords

  • chromatin immunoprecipitation
  • p53
  • p21
  • MDM2
  • PUMA
  • histone acetyltransferase
  • CELL-CYCLE ARREST
  • TRANSCRIPTIONAL ACTIVATION
  • IN-VIVO
  • CANCER CELLS
  • P53 PROTEIN
  • BINDING
  • EXPRESSION
  • COMPLEX
  • GENE
  • PHOSPHORYLATION

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