Tissue-specific methylomes reveal epigenetic memory in adult mouse tissue

Cytosine methylation of DNA is an evolutionarily conserved mechanism from plants to animals with crucial roles in gene regulation. However, the variation between methylomes of normal tissues is largely unexplored. To better understand the epigenetic variation of a normal individual, we profiled DNA methylation using whole genome bisulfite sequencing in 17 tissues isolated from an individual mouse. We observed a unique distribution of CpG methylation for each tissue, which cluster based on cell lineage. Global analysis identified only one-eighth of the genome as tissue-specifically methylated. Remarkably, the vast majority of these regions exhibit hallmarks of cis-regulatory activity. Our results also reveal a novel class of dormant enhancers in adult tissues which retain an epigenetic memory of regulatory elements active during development. Together, these results expand the repertoire of regulatory information encoded within the methylome, and suggest mapping it as an alternative method to identify cell-type specific regulatory elements. whole genome bisulfite sequencing of mouse adult tissue

DNA的胞嘧啶甲基化（Cytosine methylation）是植物至动物均保守的进化调控机制，在基因表达调控中发挥核心作用。然而，不同正常组织的甲基化组（methylomes）之间的差异尚未得到充分探索。为深入解析正常个体的表观遗传变异，我们对单只成年小鼠分离得到的17种组织，采用全基因组亚硫酸氢盐测序（whole genome bisulfite sequencing）技术表征DNA甲基化水平。研究发现，每种组织均具有独特的CpG甲基化分布特征，且该分布可依据细胞谱系进行聚类。全基因组分析仅鉴定出约八分之一的基因组区域为组织特异性甲基化位点。值得注意的是，此类区域的绝大多数均具备顺式调控活性的标志性特征。本研究还在成年组织中发现了一类新型休眠增强子，这类元件保留了发育阶段活性调控元件的表观遗传记忆。综上，本研究拓展了甲基化组所编码的调控信息范畴，并提示可将甲基化组图谱绘制作为鉴定细胞类型特异性调控元件的替代手段。小鼠成年组织全基因组亚硫酸氢盐测序