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Abstract：
DNA methylation is a crucial epigenetic mechanism in obesity and fat distribution. We explored the Sarcospan ( SSPN) gene locus by using genome-wide data sets comprising methylation and expression data, pyrosequencing analysis in the promoter region, and genetic analysis of an SNP variant rs718314, which was previously reported to associate with waist-to-hip ratio. We found that DNA methylation influences several clinical variables related to fat distribution and glucose metabolism, while SSPN mRNA levels showed directionally opposite effects on these traits. Complete DNA methylation of the SSPN promoter construct suppressed the gene expression of firefly luciferase in MCF7 cells. Moreover, rs718314 was associated with waist and with DNA methylation at CpG sites. Our data strongly support the role of the SSPN locus in body fat composition and glucose homeostasis, and suggest that this is most likely the result of changes in DNA methylation of SSPN in adipose tissue.-Keller, M., Klös, M., Rohde, K., Krüger, J., Kurze, T., Dietrich, A., Schön, M. R., Gärtner, D., Lohmann, T., Dreßler, M., Stumvoll, M., Blüher, M., Kovacs, P., Böttcher, Y. DNA methylation of SSPN is linked to adipose tissue distribution and glucose metabolism.
摘要：
DNA甲基化是肥胖和脂肪分布的重要表观遗传机制。我们通过使用包含甲基化和表达数据的全基因组数据集来探索Sarcospan（SSPN）基因位点，启动子区域的焦磷酸测序分析，和一个SNP变异体rs718314的遗传分析，以前报道该基因与腰臀比相关。我们发现DNA甲基化影响与脂肪分布和葡萄糖代谢相关的几个临床变量，而SSPNmRNA水平对这些性状显示出方向相反的影响。SSPN启动子构建体的完全DNA甲基化抑制了MCF7细胞中萤火虫荧光素酶的基因表达。此外，rs718314与腰部和CpG位点的DNA甲基化相关。我们的数据强烈支持SSPN基因座在体脂组成和葡萄糖稳态中的作用，并表明这很可能是脂肪组织中SSPNDNA甲基化变化的结果。-凯勒,M、Klös,M、罗德,K.,Krüger,J.,Kurze,T.,迪特里希,A.,舍恩,M、R、Gärtner,D.,Lohmann,T.,德雷斯勒,M、Stumvoll,M、布吕赫,M、科瓦奇,P.,Böttcher,SSPN的Y.DNA甲基化与脂肪组织分布和葡萄糖代谢有关。
