PDF(Pubmed)
Abstract：
The tree shrew (Tupaia belangeri) is a promising emerging model organism in biomedical studies, notably due to their evolutionary proximity to primates. To enhance our understanding of how DNA methylation is implicated in regulation of gene expression and the X chromosome inactivation (XCI) in tree shrew brains, here we present their first genome-wide, single-base-resolution methylomes integrated with transcriptomes from prefrontal cortices. We discovered both divergent and conserved features of tree shrew DNA methylation compared to that of other mammals. DNA methylation levels of promoter and gene body regions are negatively correlated with gene expression, consistent with patterns in other mammalian brains studied. Comparing DNA methylation patterns of the female and male X chromosomes, we observed a clear and significant global reduction (hypomethylation) of DNA methylation across the entire X chromosome in females. Our data suggests that the female X hypomethylation does not directly contribute to the gene silencing of the inactivated X chromosome nor does it significantly drive sex-specific gene expression of tree shrews. However, we identified a putative regulatory region in the 5\' end of the X inactive specific transcript (Xist) gene, a key gene for XCI, whose pattern of differential DNA methylation strongly relate to its differential expression between male and female tree shrews. We show that differential methylation of this region is conserved across different species. Moreover, we provide evidence suggesting that the observed difference between human and tree shrew X-linked promoter methylation is associated with the difference in genomic CpG contents. Our study offers novel information on genomic DNA methylation of tree shrews, as well as insights into the evolution of X chromosome regulation in mammals.
摘要：
树sh（Tupaiabelangeri）是生物医学研究中一个有前途的新兴模式生物，特别是由于它们与灵长类动物的进化接近。为了增强我们对DNA甲基化如何与树the大脑中基因表达和X染色体失活（XCI）的调节有关的理解，在这里，我们展示了他们的第一个全基因组，与前额叶皮层转录组整合的单碱基分辨率甲基化组。与其他哺乳动物相比，我们发现了树theDNA甲基化的不同和保守特征。启动子和基因体区的DNA甲基化水平与基因表达呈负相关,与其他哺乳动物大脑的模式一致。比较女性和男性X染色体的DNA甲基化模式，我们观察到女性整个X染色体DNA甲基化的明显和显著的整体减少(低甲基化).我们的数据表明，雌性X低甲基化不会直接导致失活X染色体的基因沉默，也不会显着驱动树the的性别特异性基因表达。然而,我们在X非活性特异性转录本（Xist）基因的5'末端鉴定了一个推定的调控区，XCI的关键基因，其差异DNA甲基化模式与其在雄性和雌性树sh之间的差异表达密切相关。我们表明，该区域的差异甲基化在不同物种中是保守的。此外，我们提供的证据表明，观察到的人和树shX连锁启动子甲基化之间的差异与基因组CpG含量的差异有关。我们的研究提供了有关树sh基因组DNA甲基化的新信息，以及对哺乳动物X染色体调控进化的见解。
