title: Fatty acid synthase promoter: characterization, and transcriptional regulation by sterol regulatory element binding protein-1 in goat mammary epithelial cells.
abstract: Fatty acid synthase (FASN) is the central enzyme of the de novo fatty acid biosynthesis pathway. Although the FASN transcriptional regulatory mechanism has been elucidated clearly in many tumor cells, its mechanism is still not clear in the ruminant mammary gland. In this study, we cloned and sequenced a 1.8-kb fragment of the FASN 5' flanking region from goat genomic DNA. Multiple alignment analysis demonstrated that the entire 1.8-kb fragment has little homology but that the sub-section nearest the transcriptional start site (-203 to +1) is more conserved across species, in particular the binding motifs for transcriptional regulation. Deletion analysis revealed a putative core promoter region located in -297/-14 bp upstream of the transcription site within the high homology domain. Mutations of sterol response elements (SRE1 and SRE2) and the nuclear factor Y (NF-Y) binding site appeared to significantly down-regulate the FASN promoter activity in goat mammary epithelial cells (P<0.05). Further analysis showed that both SRE sites responded to sterol regulatory element-binding protein 1 (SREBP-1). SREBP-1 overexpression and knockdown by small interference RNA influenced the abundance of endogenous FASN. These data suggested that SREBP-1 may regulate FASN expression at the transcriptional level in the lactating goat mammary gland. Hence, the current work will contribute valuable information to understanding the molecular regulatory mechanisms of FASN during lactation.
authors: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.
authors: Jun
authors: J
authors: Li
authors: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.
authors: Jun
authors: J
authors: Luo
authors: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.
authors: Huifen
authors: H
authors: Xu
authors: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.
authors: Miao
authors: M
authors: Wang
authors: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.
authors: Jiangjiang
authors: J
authors: Zhu
authors: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.
authors: Hengbo
authors: H
authors: Shi
authors: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.
authors: Abiel Berhane
authors: AB
authors: Haile
authors: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.
authors: Hui
authors: H
authors: Wang
authors: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.
authors: Yuting
authors: Y
authors: Sun
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics; D004847:Epithelial Cells; D054890:Fatty Acid Synthase, Type I / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006041:Goats; D007774:Lactation / Q000235:genetics* / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D023081:CCAAT-Binding Factor; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; C402244:nuclear factor Y; D054890:Fatty Acid Synthase, Type I
keywords: Fatty acid synthase promoter; Lipogenesis; Sterol regulatory element binding protein-1; Transcriptional regulation