Cell-Specific Polymorphism and Hormonal Regulation of DNA Methylation in Scavenger Receptor Class B, Type I
Cell-Specific Polymorphism and Hormonal Regulation of DNA Methylation in Scavenger Receptor Class B, Type I
复制标题
清道夫受体 B 类、I 型 DNA 甲基化的细胞特异性多态性和激素调节
DOI：
10.1089/dna.2015.3185
复制
发表时间：
2016-06-01
影响因子：
3.1
通讯作者：
Guo, Zhigang
中科院分区：
文献类型：
--
作者：
Hu, Zhigang;Li, Jiaxin;Guo, Zhigang
清道夫受体B类，I型(SR-BI)是一种细胞表面糖蛋白，介导高密度脂蛋白(HDL)衍生的胆固醇酯的选择性摄取。SR-BI在胆固醇的细胞转运中起着重要作用。人和啮齿动物的SR-BI都在肝实质细胞和肾上腺、性腺的类固醇生成细胞中大量表达，选择性途径在这些细胞中表现出最高的活性。在类固醇生成细胞中，SR-BI的表达受营养激素(促肾上腺皮质激素或促性腺激素、黄体生成素或卵泡刺激素)的调节，与类固醇激素的产生调节相一致。DNA甲基化参与了许多生物学过程，主要是通过调控基因表达。SR-BI启动子包含1个CpG岛(CGI)和7个CGI内含子。在这里，我们研究了SR-BI基因的DNA甲基化状态，并提供了该基因启动子和内含子区域DNA甲基化具有细胞特异性的证据。在小鼠肾上腺Y1细胞和小鼠间质肿瘤细胞(MLTCs)中，SR-BI启动子的DNA甲基化受N-6，2‘-O-二丁基腺苷3’：5‘-环一磷酸的调节。这7个内含子CGI在Y1细胞、MLTC、卵巢颗粒细胞和小鼠肝脏HEPA 1-6细胞中存在差异甲基化。我们的实验提出了DNA甲基化以组织特异性的方式参与激素调节SR-BI表达的可能性。我们进一步认为，SR-BI内含子区域的细胞特异性甲基化可能与这些区域的特定生物学功能(S)有关，包括对基因表达的调控。
The scavenger receptor class B, type I (SR-BI), is a cell-surface glycoprotein that mediates selective uptake of high density lipoprotein (HDL)-derived cholesteryl ester. SR-BI plays an important role in cellular delivery of cholesterol. Both human and rodent SR-BI are expressed most abundantly in the liver parenchymal cells and steroidogenic cells of the adrenal gland and gonads, where the selective pathway exhibits its highest activity. In steroidogenic cells, the expression of SR-BI is regulated by trophic hormones (adrenocorticotropic hormone or gonadotropins luteinizing hormone or follicle-stimulating hormone) in concert with the regulation of steroid hormone production. DNA methylation has been implicated in a large number of biological processes mainly by regulating gene expression. The SR-BI promoter contains one CpG island (CGI) in its promoter and seven CGIs in its intronic regions. Here, we studied the DNA methylation status of SR-BI gene and provide evidence that the DNA methylation is cell specific in this gene promoter as well as in intronic regions. The DNA methylation in the SR-BI promoter is subject to N-6,2'-O-dibutyryladenosine3':5'-cyclic monophosphate regulation in mouse adrenal Y1 cells and mouse Leydig tumor cells (MLTCs). The seven intron CGIs are methylated differentially in Y1 cells, MLTCs, ovarian granulosa cells, and mouse liver hepa 1-6 cells. Our experiments raised the possibility that DNA methylation participates in hormonal regulation of SR-BI expression in a tissue-specific manner. We further suggest that the cell-specific DNA methylation in SR-BI intronic regions may be associated with specific biological function(s) of these regions, including regulation of gene expression.