DNA methylation Landscape of body size variation in sheep.

DNA methylation Landscape of body size variation in sheep.
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DOI:
10.1038/srep13950
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发表时间:
2015-10-16
期刊:
影响因子:
4.6
通讯作者:
Du L
Du L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cao J;Wei C;Liu D;Wang H;Wu M;Xie Z;Capellini TD;Zhang L;Zhao F;Li L;Zhong T;Wang L;Lu J;Liu R;Zhang S;Du Y;Zhang H;Du L

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中国蒙古羊亚群在体重上表现出显著差异。在本研究中,我们对这些品种的全基因组DNA甲基化进行了测序,通过甲基化DNA免疫沉淀-测序法检测DNA甲基化是否在绵羊体重决定中起作用。本研究获得了高质量的中国蒙古羊甲基化图谱。我们确定了位于93个人类同源物中的399个不同的甲基化区域,这些区域先前在人类全基因组关联研究中被报道为体型相关基因。我们测试了LTBP1的三个区域,发现两个CpG位点的DNA甲基化与其RNA表达有显著相关性。此外,一组在“发育过程”中富集的差异甲基化窗口(GO: 0032502)被确定为与体重变化相关的潜在候选者。接下来,我们在5个基因中验证了这些窗口的一小部分;SMAD1、TSC1和AKT1的DNA甲基化在不同品种间存在显著差异,6个CpG与RNA表达显著相关。有趣的是,两个CpG位点与TSC1蛋白表达显著相关。本研究从表观遗传学的角度对绵羊体型的变化进行了深入的研究。
Sub-populations of Chinese Mongolian sheep exhibit significant variance in body mass. In the present study, we sequenced the whole genome DNA methylation in these breeds to detect whether DNA methylation plays a role in determining the body mass of sheep by Methylated DNA immunoprecipitation – sequencing method. A high quality methylation map of Chinese Mongolian sheep was obtained in this study. We identified 399 different methylated regions located in 93 human orthologs, which were previously reported as body size related genes in human genome-wide association studies. We tested three regions in LTBP1, and DNA methylation of two CpG sites showed significant correlation with its RNA expression. Additionally, a particular set of differentially methylated windows enriched in the “development process” (GO: 0032502) was identified as potential candidates for association with body mass variation. Next, we validated small part of these windows in 5 genes; DNA methylation of SMAD1, TSC1 and AKT1 showed significant difference across breeds, and six CpG were significantly correlated with RNA expression. Interestingly, two CpG sites showed significant correlation with TSC1 protein expression. This study provides a thorough understanding of body size variation in sheep from an epigenetic perspective.