Properties of overlapping EREs: synergistic activation of transcription and cooperative binding of ER

Biochemistry
Charbel MassaadRobert Barouki

Abstract

We have designed a novel estrogen-responsive unit, overERE, which consists of two overlapping ERE separated by 5 bp (center-to-center). In gel retardation assays, this sequence forms a low-mobility complex that migrates like an estrogen receptor tetramer. The receptor-overERE complex was specific and was supershifted by anti-ER H222 antibodies. Dose response studies showed that the formation of the receptor tetramer-overERE complex was cooperative. Truncated receptors were used to assess the contribution of the receptor domains. Deletion of the E domain of the ER prevented the formation of an ER-tetramer complex, which reflects a novel function of this receptor domain. In transfection experiments, 17-beta-estradiol activated transcription from an overERE-containing promoter 4-6 times better than from an ERE-containing promoter. This synergistic effect was observed using either the natural hormone (17-beta-estradiol) or xenoestrogens (phenol red, chlordane). We conclude that two overlapping estrogen-responsive elements can elicit synergistic induction of transcription.

Citations

Mar 17, 2005·Breast Cancer Research and Treatment·Richard A CassidyGeorge M Vaughan
Jul 14, 2001·Nucleic Acids Research·C M Klinge
Jun 24, 1999·Environmental Health Perspectives·C Massaad, R Barouki
Sep 28, 2005·Proceedings of the National Academy of Sciences of the United States of America·Cosima FonteCharbel Massaad
May 4, 2007·The Journal of Steroid Biochemistry and Molecular Biology·Cosima FonteCharbel Massaad
May 29, 2002·General and Comparative Endocrinology·Joël RousseauMaria-Grazia Martinoli
Oct 4, 2011·Biophysical Journal·Floriane Nicol-BenoitDenis Michel
Dec 18, 2002·Annals of the New York Academy of Sciences·Francoise CadepondMichael Schumacher
May 15, 2007·The Journal of Pharmacology and Experimental Therapeutics·Thierry BordetRebecca M Pruss

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