Constitutive DNase I hypersensitivity of p53-regulated promoters.
The ability of p53 to alter, at the transcriptional level, the gene expression of downstream targets is critical for its role as a tumor suppressor. Most models of p53 activation postulate the stepwise recruitment by p53 of coactivators, histone acetyltransferases, and/or chromatin remodeling factors to a promoter region to facilitate the subsequent access of the general transcriptional machinery required for transcriptional induction. We demonstrate here, however, that the promoter regions for the p53 target genes, p21, 14-3-3sigma, and KARP-1, exist in a constitutively open conformation that is readily accessible to DNase I. This conformation was not altered by DNA damage or by whether p53 was present or absent in the cell. In contrast, p53 response elements, which resided outside the immediate promoter regions, existed within DNase I-resistant chromatin domains. Thus, p53 activation of downstream target genes occurs without p53 inducing chromatin alterations detectable by DNase I accessibility at either the promoter or the response element. As such, these data support models of p53 activation that do not require extensive chromatin alterations to support cognate gene expression.
Braastad
Corey D
CD
Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
Han
Zhiyong
Z
Hendrickson
Eric A
EA
D048948:14-3-3 Proteins; D001483:Base Sequence; D014408:Biomarkers, Tumor; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004265:DNA Helicases; D017931:DNA Primers; D003850:Deoxyribonuclease I / Q000378:metabolism*; D005092:Exonucleases / Q000235:genetics; D005095:Exoribonucleases; D007259:Infrared Rays; D000072200:Ku Autoantigen; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000528:radiation effects
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D003850:Deoxyribonuclease I; D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen