title: Functional Characterization of Exonic Variants of the PPARGC1B Gene in Coregulation of Estrogen Receptor Alpha.
abstract: Peroxisome proliferator-activated receptor gamma coactivator 1 beta (PPARGC1B) is a coactivator of estrogen receptor (ER)α and ERβ. We previously demonstrated a significant association between a variant of exon 5 of the PPARGC1B gene (+102525 G>A, R265Q) and airway hyperreactivity (AHR). The aims of the study were to evaluate the genetic effects of variants of the PPARGC1B gene on the function of ERs. PPARGC1B +102525G and A gene constructs were generated using PCR and cloned into a pCMV4 promoter vector. A luciferase reporter assay was undertaken in 293T cells cotransfected with one of the PPARGC1B +102525G>A constructs, ERα, and an estrogen response element (ERE) containing a luciferase construct after treatment with 17β-estradiol. According to the luciferase reporter assay, the +102525A allele showed higher ERα activity than the +102525G allele in response to stimulation with 17β-estradiol. In addition, the interaction between ERα and PPARGC1B was evaluated by coprecipitation assay. Human influenza hemagglutinin-tagged PPARGC1B coprecipitated more intensely with ERα in the +102525A than the +102525G construct after 17β estradiol treatment. The variant +102525A allele enhances the activity of ERα to a greater degree than the +102525G allele of PPARGC1B.
authors.affiliation: 1 Department of Medical Bioscience, Graduate School, Soonchunhyang University , Asan, Republic of Korea.
authors.forename: Hun Soo
authors.initials: HS
authors.lastname: Chang
authors.affiliation: 1 Department of Medical Bioscience, Graduate School, Soonchunhyang University , Asan, Republic of Korea.
authors.forename: Shin-Hwa
authors.initials: SH
authors.lastname: Lee
authors.affiliation: 1 Department of Medical Bioscience, Graduate School, Soonchunhyang University , Asan, Republic of Korea.
authors.forename: Jong-Uk
authors.initials: JU
authors.lastname: Lee
authors.affiliation: 2 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital , Bucheon, Republic of Korea.
authors.forename: Jong Sook
authors.initials: JS
authors.lastname: Park
authors.affiliation: 3 Division of Molecular and Life Sciences, College of Science and Technology, Hanyang University , Ansan, Republic of Korea.
authors.forename: Il Yup
authors.initials: IY
authors.lastname: Chung
authors.affiliation: 1 Department of Medical Bioscience, Graduate School, Soonchunhyang University , Asan, Republic of Korea.|2 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital , Bucheon, Republic of Korea.
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D006801:Humans; D047495:PPAR gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D047495:PPAR gamma; C455622:PPARGC1B protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D004958:Estradiol