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α-生育酚调节影响牛细胞基本生物学过程的转录活性。

Alpha-Tocopherol Modulates Transcriptional Activities that Affect Essential Biological Processes in Bovine Cells.

作者信息

Li Cong-Jun, Li Robert W, Elsasser Theodore H

机构信息

Bovine Functional Genomics Laboratory, Animal and Natural Resources Institute, ARS, USDA, 10300 Baltimore Ave, Beltsville, MD, 20705, USA.

出版信息

Gene Regul Syst Bio. 2010 Nov 22;4:109-24. doi: 10.4137/GRSB.S6007.

Abstract

Using global expression profiling and pathway analysis on α-tocopherol-induced gene perturbation in bovine cells, this study has generated comprehensive information on the physiological functions of α-tocopherol. The data confirmed α-tocopherol is a potent regulator of gene expression and α-tocopherol possesses novel transcriptional activities that affect essential biological processes. The genes identified fall within a broad range of functional categories and provide the molecular basis for its distinctive effects. Enrichment analyses of gene regulatory networks indicate α-tocopherol alter the canonical pathway of lipid metabolism and transcription factors SREBP1 and SREBP2, (Sterol regulatory element binding proteins), which mediate the regulatory functions of lipid metabolism. Transcription factors HNF4-α (Hepatocyte nuclear factor 4), c-Myc, SP1 (Sp1 transcription factor), ESR1 (estrogen receptor 1, nuclear), and androgen receptor, along with several others, were centered as the hubs of transcription regulation networks. The data also provided direct evidence that α-tocopherol is involved in maintaining immuno-homeostasis through targeting the C3 (Complement Component 3) gene.

摘要

通过对牛细胞中α-生育酚诱导的基因扰动进行全基因组表达谱分析和通路分析,本研究生成了关于α-生育酚生理功能的全面信息。数据证实α-生育酚是基因表达的有效调节剂,且α-生育酚具有影响重要生物学过程的新型转录活性。鉴定出的基因属于广泛的功能类别,并为其独特作用提供了分子基础。基因调控网络的富集分析表明,α-生育酚改变了脂质代谢的经典途径以及介导脂质代谢调节功能的转录因子SREBP1和SREBP2(固醇调节元件结合蛋白)。转录因子HNF4-α(肝细胞核因子4)、c-Myc、SP1(Sp1转录因子)、ESR1(雌激素受体1,核)和雄激素受体等,以及其他一些因子,是转录调控网络的核心枢纽。数据还提供了直接证据,表明α-生育酚通过靶向C3(补体成分3)基因参与维持免疫稳态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ad/3001320/8e6e6736a569/grsb-2010-109f1.jpg

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