title: Regulation of transcriptional activation function of rat estrogen receptor α (ERα) by novel C-terminal splice inserts.
abstract: Estrogen receptor α (ERα) mediates estrogen diverse actions on tissues. ERα gene has eight constitutively expressing exons and is known to have multiple isoforms generated by alternative initiation of transcription and splicing events including exon skipping. We have discovered two novel exons inserted between exon 5 and 6 of rat ERα that can add independently or in tandem 18 and 14 amino acids to the estrogen binding/activator function 2 domain of the receptor. Their transcript expression is three to six fold higher in heart compared to brain, aorta, liver, ovary and uterus. In heart, the new variants increased ~2 fold with animal growth from prenatal to adulthood, and had a minor increment in aged animals (28 months). Inclusion of these exons yields a receptor with practically no binding capacity for estrogen and reduced dimerization. The new variants show nuclear localization but are less efficient in binding to estrogen responsive elements (EREs) and failed to transcriptionally activate promoters containing EREs (mSlo, KCNE2). Thus, the new variants can regulate the wild-type receptor function and may contribute to the regulatory action of estrogen, especially in the maturing heart where they are more abundant.
authors.affiliation: Department of Anesthesiology, University of California, Los Angeles, CA 90095, USA; Division of Plant Biology, Bose Institute, Kolkata 700054, India. Electronic address: pkundu@jcbose.ac.in.
authors.forename: Pallob
authors.initials: P
authors.lastname: Kundu
authors.affiliation: Department of Anesthesiology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, University of California, Los Angeles, CA 90095, USA; Department of Physiology, University of California, Los Angeles, CA 90095, USA; Department of Brain Research Institute, University of California, Los Angeles, CA 90095, USA; Department of Cardiovascular Research Laboratory, University of California, Los Angeles, CA 90095, USA.
authors.forename: Enrico
authors.initials: E
authors.lastname: Stefani
authors.affiliation: Department of Anesthesiology, University of California, Los Angeles, CA 90095, USA; Department of Brain Research Institute, University of California, Los Angeles, CA 90095, USA; Department of Cardiovascular Research Laboratory, University of California, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Ligia
authors.initials: L
authors.lastname: Toro
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008297:Male; D016254:Mutagenesis, Insertional; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D059368:RNA Isoforms / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D059368:RNA Isoforms
keywords: Alternative splicing; Estrogen receptor; Heart; Steroid receptor coactivator; Transcription regulation