title: Human stearoyl-CoA desaturase 1 (SCD-1) gene expression is negatively regulated by thyroid hormone without direct binding of thyroid hormone receptor to the gene promoter.
abstract: Stearoyl-CoA desaturase-1 (SCD-1) plays a pivotal role in an increase of triglyceride by an excess of dietary carbohydrate intake. Dietary carbohydrates increase SCD-1 gene expression in liver by sterol response element binding protein (SREBP)-1c-dependent and SREBP-1c -independent pathways. Previous report demonstrated that thyroid hormone (TH) negatively regulates mouse SCD-1 gene promoter before SREBP-1c was revealed. We reported that TH negatively regulates SREBP-1c recently. Therefore, in the current study, we examined whether and how TH regulates human SCD-1 gene expression and evaluated SREBP-1c effect on the negative regulation. Luciferase assays revealed that TH suppresses both mouse and human SCD-1 gene promoter activity. In SREBP-1 knockdown HepG2 cells, TH still suppresses SCD-1 gene promoter activity, and it also exerted the negative regulation under cotransfection of a small amount of SREBP-1c. These data indicated that SREBP-1c does not play the decisive role for the negative regulation by TH. The responsible region for the negative regulation in human SCD-1 gene promoter turned out to be between -124 and -92 bp, referred to as site A. Chromatin immunoprecipitation assays demonstrated that TH receptor-β is recruited to the region upon T(3) administration, although TR-β does not bind directly to site A. In conclusion, TH negatively regulates human SCD-1 gene expression in without direct binding of the TH receptor to the SCD-1 gene promoter.
authors.affiliation: 3-39-22 Showa-machi, Maebashi, Gunma, Japan 371-8511. khashimo@gunma-u.ac.jp
authors.forename: Koshi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Emi
authors.initials: E
authors.lastname: Ishida
authors.forename: Atsuko
authors.initials: A
authors.lastname: Miura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ozawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shibusawa
authors.forename: Teturou
authors.initials: T
authors.lastname: Satoh
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000818:Animals; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*; D013963:Thyroid Hormones / Q000494:pharmacology*
chemical_list: D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D003609:Dactinomycin; D003513:Cycloheximide; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase