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Ets1 is required for p53 transcriptional activity in UV‐induced apoptosis in embryonic stem cells
Author(s) -
Xu Dakang,
Wilson Trevor J.,
Chan David,
De Luca Elisabetta,
Zhou Jiong,
Hertzog Paul J.,
Kola Ismail
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf413
Subject(s) - biology , embryonic stem cell , apoptosis , stem cell , microbiology and biotechnology , ets1 , genetics , cancer research , transcription factor , gene
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.