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  • The EMBO Journal (2002) 21, 4081 - 4093
  • doi:10.1093/emboj/cdf413

Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells

Dakang Xu1, Trevor J. Wilson1, David Chan1, Elisabetta De Luca1, Jiong Zhou1, Paul J. Hertzog1 and Ismail Kola1,2

  1. Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, 246 Clayton, Clayton, Victoria 3168, Australia
  2. Present address: 7245-24-110, Pharmacia and Upjohn, 301 Henrietta Street, Kalamazoo, MI 39007, USA

Correspondence to:

Paul J. Hertzog, E-mail: paul.hertzog@med.monash.edu.au

Received 29 November 2001; Accepted 13 June 2002; Revised 9 May 2002

Embryonic stem (ES) cells contain a p53-dependent apoptosis mechanism to avoid the continued proliferation and differentiation of damaged cells. We show that mouse ES cells lacking Ets1 are deficient in their ability to undergo UV-induced apoptosis, similar to p53 null ES cells. In Ets1-/- ES cells, UV induction of the p53 regulated genes mdm2, perp, cyclin G and bax was decreased both at mRNA and protein levels. While p53 protein levels were unaltered in Ets1-/- cells, its ability to transactivate genes such as mdm2 and cyclin G was reduced. Furthermore, electrophoretic mobility shift assays and immunoprecipitations demonstrated that the presence of Ets1 was necessary for a CBP/p53 complex to be formed. Chromatin immunoprecipitations demonstrated that Ets1 was required for the formation of a stable p53–DNA complex under physiological conditions and activation of histone acetyltransferase activity. These data demonstrate that Ets1 is an essential component of a UV-responsive p53 transcriptional activation complex in ES cells and suggests that Ets1 may contribute to the specificity of p53-dependent gene transactivation in distinct cellular compartments.

  • Keywords:

    • apoptosis,
    • CBP,
    • Ets1,
    • p53,
    • UV