title: Sterol regulatory element binding protein-1 (SREBP-1)c promoter: Characterization and transcriptional regulation by mature SREBP-1 and liver X receptor α in goat mammary epithelial cells.
abstract: Sterol regulatory element binding protein-1 (SREBP-1) is a key transcription factor that regulates lipogenesis in rodent liver. Two isoforms (SREBP-1a and SREBP-1c) of SREBP-1 are transcribed by an alternative promoter on the same gene (SREBF1), and the isoforms differ only in their first exon. Although the regulatory effects of SREBP-1 on lipid and milk fat synthesis have received much attention in ruminants, SREBP-1c promoter and its regulatory mechanisms have not been characterized in the goat. In the present study, we cloned and sequenced a 2,012-bp fragment of the SREBP-1c 5'-flanking region from goat genomic DNA. A luciferase reporter assay revealed that SREBP-1c is transcriptionally activated by the liver X receptor α (LXRα) agonist T0901317, and is decreased by SREBP-1 small interfering (si)RNA. A 5' deletion analysis revealed a core promoter region located -395 to +1 bp upstream of the transcriptional start site (TSS). Site-directed mutagenesis of LXRα binding elements (LXRE1 and LXRE2) and sterol regulatory elements (SRE1 and SRE2) revealed that the full effects of T 4506585 require the presence of both LXRE and SRE. We also characterized a new SRE (SRE1) and demonstrated a direct role of SREBP-1 (auto-loop regulation) in maintaining its basal transcription activity. Results suggest that goat SREBP-1c gene is transcriptionally regulated by mature SREBP-1 (auto-loop circuit regulation) and LXRα in goat mammary epithelial cells.
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A & F University, Yangling, 712100, PR China.
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, 712100, PR China. Electronic address: luojun@nwsuaf.edu.cn.
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors.forename: H P
authors.initials: HP
authors.lastname: Wang
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A & F University, Yangling, 712100, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A & F University, Yangling, 712100, PR China.
authors.forename: T Y
authors.initials: TY
authors.lastname: Zhang
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A & F University, Yangling, 712100, PR China.
authors.forename: H B
authors.initials: HB
authors.lastname: Tian
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A & F University, Yangling, 712100, PR China.
authors.forename: D W
authors.initials: DW
authors.lastname: Yao
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; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006041:Goats / Q000235:genetics* / Q000378:metabolism; D000071518:Liver X Receptors / Q000235:genetics* / Q000378:metabolism; D008321:Mammary Glands, Animal; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034741:RNA, Small Interfering; D017422:Sequence Analysis, DNA / Q000662:veterinary; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000071518:Liver X Receptors; D034741:RNA, Small Interfering; D051780:Sterol Regulatory Element Binding Protein 1
keywords: liver X receptor α (LXRα); milk fat; sterol regulatory element binding protein-1c (SREBP-1c); transcription regulation