Interplay between estrogen response element sequence and ligands controls in vivo binding of estrogen receptor to regulated genes.

Article Details

Citation

Krieg AJ, Krieg SA, Ahn BS, Shapiro DJ

Interplay between estrogen response element sequence and ligands controls in vivo binding of estrogen receptor to regulated genes.

J Biol Chem. 2004 Feb 6;279(6):5025-34. Epub 2003 Nov 14.

PubMed ID
14617632 [ View in PubMed
]
Abstract

To examine the role of the estrogen response element (ERE) sequence in binding of liganded estrogen receptor (ER) to promoters, we analyzed in vivo interaction of liganded ER with the imperfect ERE in the pS2 gene and the composite estrogen-responsive unit (ERU) in the proteinase inhibitor 9 (PI-9) gene. In transient transfections of ER-positive HepG2-ER7 cells, PI-9 was strongly induced by estrogen, moxestrol (MOX), and 4-hydroxytamoxifen (OHT). PI-9 was not induced by raloxifene or ICI 182,780. Quantitative reverse transcriptase-PCR showed that moxestrol strongly induced cellular PI-9 and pS2 mRNAs, whereas OHT moderately induced PI-9 mRNA and weakly induced pS2 mRNA. Chromatin immunoprecipitation experiments demonstrated strong and similar association of 17beta-estradiol-hERalpha and MOX-hERalpha with the PI-9 ERU and with the pS2 ERE. Binding of MOX-hERalpha to the PI-9 ERU and the pS2 ERE was rapid and continuous. Although MOX-hERalpha bound strongly to the PI-9 ERU and less well to the pS2 ERE in chromatin immunoprecipitation, gel shift assays showed that estrogen-hERalpha binds with higher affinity to the deproteinized pS2 ERE than to the PI-9 ERU. Across a broad range of OHT concentrations, OHT-hERalpha associated strongly with the pS2 ERE and weakly with the PI-9 ERU. ICI-hERalpha bound poorly to the PI-9 ERU and effectively to the pS2 ERE. Raloxifene-hERalpha and MOX-hERalpha exhibited similar binding to the PI-9 ERU and the pS2 ERE. These studies demonstrate that ER ligand and ERE sequence work together to regulate in vivo binding of ER to estrogen-responsive promoters.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AfimoxifeneTrefoil factor 1ProteinHumans
Unknown
Not AvailableDetails
RaloxifeneSerpin B9ProteinHumans
Unknown
Not AvailableDetails
RaloxifeneTrefoil factor 1ProteinHumans
Unknown
Not AvailableDetails
Pharmaco-transcriptomics
DrugDrug GroupsGeneGene IDChangeInteractionChromosome
AfimoxifeneInvestigationalSERPINB95272
upregulated
afimoxifene results in increased expression of SERPINB9 mRNA6p25.2
AfimoxifeneInvestigationalTFF17031
upregulated
afimoxifene results in increased expression of TFF1 mRNA21q22.3