title: Characterization of the liver X receptor-dependent regulatory mechanism of goat stearoyl-coenzyme A desaturase 1 gene by linoleic acid.
abstract: Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in the biosynthesis of palmitoleic and oleic acid. Although the transcriptional regulatory mechanism of SCD1 via polyunsaturated fatty acids (PUFA) has been extensively explored in nonruminants, the existence of such mechanism in ruminant mammary gland remains unknown. In this study, we used goat genomic DNA to clone and sequence a 1,713-bp fragment of the SCD1 5' flanking region. Deletion assays revealed a core region of the promoter located between -415 and -109 bp upstream of the transcription start site, and contained the highly conserved PUFA response region. An intact PUFA response region was required for the basal transcriptional activity of SCD1. Linoleic acid reduced endogenous expression of SCD1 and sterol regulatory element binding factor-1 (SREBF1) in goat mammary epithelial cells. Further analysis indicated that both the sterol response element (SRE) and the nuclear factor Y (NF-Y) binding site in the SCD1 promoter were responsible for the inhibition effect by linoleic acid, whereas the effect was abrogated once NF-Y was deleted. In addition, SRE and NF-Y were partly responsible for the transcriptional activation induced via the liver X receptor agonist T 4506585 (Sigma-Aldrich, St. Louis, MO). When goat mammary epithelial cells were cultured with linoleic acid, addition of T 4506585 markedly increased SCD1 transcription in controls, but had no effect on cells with a deleted SRE promoter. These results demonstrated that linoleic acid can regulate SCD1 expression at the transcriptional level through SRE and NF-Y in a liver X receptor-dependent fashion in the goat mammary gland.
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, P. R. China 712100.
authors.forename: D W
authors.initials: DW
authors.lastname: Yao
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, P. R. China 712100. Electronic address: luojun@nwsuaf.edu.cn.
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, P. R. China 712100.
authors.forename: Q Y
authors.initials: QY
authors.lastname: He
authors.affiliation: College of Animal Science and Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, P. R. China 450046.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, P. R. China 712100.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Animal Sciences, Zhejiang Sci-Tech University, Hangzhou, P. R. China 310058.
authors.forename: H B
authors.initials: HB
authors.lastname: Shi
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, P. R. China 712100.
authors.forename: H F
authors.initials: HF
authors.lastname: Xu
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, P. R. China 712100.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana 61801. Electronic address: jloor@illinois.edu.
authors.forename: J J
authors.initials: JJ
authors.lastname: Loor
mesh_terms: D000818:Animals; D001483:Base Sequence; D006041:Goats / Q000378:metabolism*; D019787:Linoleic Acid; D000071518:Liver X Receptors; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics
chemical_list: D000071518:Liver X Receptors; D051780:Sterol Regulatory Element Binding Protein 1; D019787:Linoleic Acid; D013230:Stearoyl-CoA Desaturase
keywords: SREBF1; linoleic acid; stearoyl-CoA desaturase 1 promoter; transcriptional regulation