Functional Characterization of Exonic Variants of the PPARGC1B Gene in Coregulation of Estrogen Receptor Alpha

Title
Functional Characterization of Exonic Variants of the PPARGC1B Gene in Coregulation of Estrogen Receptor Alpha
Author
정일엽
Keywords
SINGLE-NUCLEOTIDE POLYMORPHISMS; COACTIVATOR 1-BETA PGC-1-BETA; TYPE-2 DIABETES-MELLITUS; SMOOTH-MUSCLE; AIRWAY HYPERRESPONSIVENESS; TRANSCRIPTION FACTORS; SKELETAL-MUSCLE; MENSTRUAL-CYCLE; DOWN-REGULATION; IN-VIVO
Issue Date
2016-05
Publisher
MARY ANN LIEBERT
Citation
DNA AND CELL BIOLOGY, v. 35, NO 7, Page. 314-321
Abstract
Peroxisome proliferator-activated receptor gamma coactivator 1 beta (PPARGC1B) is a coactivator of estrogen receptor (ER)alpha and ER beta. 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, ER alpha, and an estrogen response element (ERE) containing a luciferase construct after treatment with 17 beta-estradiol. According to the luciferase reporter assay, the +102525A allele showed higher ER alpha activity than the +102525G allele in response to stimulation with 17 beta-estradiol. In addition, the interaction between ER alpha and PPARGC1B was evaluated by coprecipitation assay. Human influenza hemagglutinin-tagged PPARGC1B co-precipitated more intensely with ER alpha in the +102525A than the +102525G construct after 17 beta estradiol treatment. The variant +102525A allele enhances the activity of ER alpha to a greater degree than the +102525G allele of PPARGC1B.
URI
https://www.liebertpub.com/doi/10.1089/dna.2015.3195http://hdl.handle.net/20.500.11754/64737
ISSN
1044-5498; 1557-7430
DOI
10.1089/dna.2015.3195
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GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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