Constitutive DNase I hypersensitivity of p53-regulated promoters

Corey D. Braastad, Zhiyong Han, Eric A. Hendrickson

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 co-activators, 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, 14-3-3σ, 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.

Original languageEnglish (US)
Pages (from-to)8261-8268
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number10
DOIs
StatePublished - Mar 7 2003

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Deoxyribonuclease I
Genetic Promoter Regions
Chromatin
Hypersensitivity
Response Elements
Chemical activation
Gene expression
Histone Acetyltransferases
Conformations
Gene Expression
Chromatin Assembly and Disassembly
Genes
p53 Genes
DNA Damage
Machinery
Tumors
DNA
Neoplasms

Cite this

Constitutive DNase I hypersensitivity of p53-regulated promoters. / Braastad, Corey D.; Han, Zhiyong; Hendrickson, Eric A.

In: Journal of Biological Chemistry, Vol. 278, No. 10, 07.03.2003, p. 8261-8268.

Research output: Contribution to journalArticle

Braastad, Corey D. ; Han, Zhiyong ; Hendrickson, Eric A. / Constitutive DNase I hypersensitivity of p53-regulated promoters. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 10. pp. 8261-8268.
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