AP2α and AP2γ: a comparison of binding site specificity and trans-activation of the estrogen receptor promoter and single site promoter constructs

Lisa A McPherson; Ronald J Weigel

doi:10.1093/nar/27.20.4040

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AP2α and AP2γ: a comparison of binding site specificity and trans-activation of the estrogen receptor promoter and single site promoter constructs

Journal article

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Peer reviewed

AP2α and AP2γ: a comparison of binding site specificity and trans-activation of the estrogen receptor promoter and single site promoter constructs

Lisa A McPherson and Ronald J Weigel

Nucleic acids research, Vol.27(20), pp.4040-4049

10/15/1999

DOI: 10.1093/nar/27.20.4040

PMID: 10497269

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Abstract

The AP2 transcription factors exhibit a high degree of homology in the DNA binding and dimerization domains. In this study, we methodically compared the binding specificity of AP2 alpha and AP2 gamma using PCR-assisted binding site selection and competitive gel shift assay and determined that the consensus binding site for both factors is G/CCCNN super(A/)C sub(/G) super(G)/ sub(A)G super(G/)C sub(/T). The use of single site promoter constructs with either a high or low affinity site demonstrated a direct relationship between site affinity and transcriptional activation. Overexpression of AP2 alpha and AP2 gamma resulted in the activation of a low affinity binding site construct to levels comparable to those seen with a high affinity site construct at lower amounts of protein expression. Both AP2 alpha and AP2 gamma were able to trans-activate the cloned human estrogen receptor alpha promoter in ER-negative MDA-MB-231 cells through high affinity AP2 sites in the untranslated leader sequence. This provides a functional mechanism to explain the correlation between AP2 activity and estrogen receptor expression in breast cancer. Since there is overexpression of AP2 factors in breast cancer compared to normal breast epithelium, our results suggest that increased factor expression may activate a set of target genes containing lower affinity binding sites that would normally not be expressed in normal breast epithelium.

AP-2 protein

breast carcinoma

estrogen receptors

Details

Title: Subtitle: AP2α and AP2γ: a comparison of binding site specificity and trans-activation of the estrogen receptor promoter and single site promoter constructs
Creators: Lisa A McPherson
Ronald J Weigel
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.27(20), pp.4040-4049
DOI: 10.1093/nar/27.20.4040
PMID: 10497269
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Language: English
Date published: 10/15/1999
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984025286902771

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