title: Transcription factor GATA-6 recruits PPARα to cooperatively activate Glut4 gene expression.
abstract: Peroxisome proliferator-activated receptor α (PPARα) is a nuclear hormone receptor that regulates energy metabolism, but its precise mechanisms remain unknown. Here, we demonstrate that the PPARα agonist fenofibrate activated expression of the glucose transporter Glut4. Moreover, PPARα was associated with the Glut4 promoter through GATA sites upon fenofibrate stimulation in cardiomyocytes. This occupancy is achieved through an interaction between amino acids 1-136 of PPARα with amino acids 276-443 of the cardiac transcription factor GATA-6. In addition, the interaction of PPARα with GATA-6 activated Glut4 gene expression, improved glucose consumption, and enhanced activity of mitochondrial citrate synthase in C2C12 myoblasts; both mutants of PPARα (1-101 aa) and GATA-6 (227-331 aa) were unable to cooperate in Glut4 activation. Thus, GATA-6 is an important component of the transcription network required for energy metabolism mediated by PPARα, and these findings provide a molecular basis for understanding the role of GATA-6 proteins in muscle development and disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou City, Henan 450001, China.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yao
authors.forename: Cheng-Juan
authors.initials: CJ
authors.lastname: Xiong
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
authors.forename: Fen
authors.initials: F
authors.lastname: Yang
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhang
authors.forename: Tian-qi
authors.initials: TQ
authors.lastname: Wang
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Wang
authors.forename: Huan-Ling
authors.initials: HL
authors.lastname: Yu
authors.forename: Zhi-Ru
authors.initials: ZR
authors.lastname: Wei
authors.forename: Ming-Xi
authors.initials: MX
authors.lastname: Zang
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology; D050993:GATA6 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D041681:NIH 3T3 Cells; D047493:PPAR alpha / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000596:Amino Acids; D050993:GATA6 Transcription Factor; D051275:Glucose Transporter Type 4; D047493:PPAR alpha; D002950:Citrate (si)-Synthase; D005947:Glucose; D011345:Fenofibrate