Characterization of universal features of partially methylated domains across tissues and species.
Characterization of universal features of partially methylated domains across tissues and species.
复制标题
跨组织和物种的部分甲基化结构域的普遍特征的特征。
DOI：
10.1186/s13072-020-00363-7
复制
发表时间：
2020-10-02
影响因子：
3.9
通讯作者：
Smith AD
中科院分区：
文献类型：
--
作者：
Decato BE;Qu J;Ji X;Wagenblast E;Knott SRV;Hannon GJ;Smith AD
部分甲基化结构域（PMD）是表观基因组在可重复和特定生物学背景下的标志，包括癌细胞、胎盘和培养细胞系。现有的用于决定PMD是否存在于样品中以及它们的鉴定的方法很少，通常针对特定的生物学问题，并且需要高覆盖率的样品以进行准确鉴定。在这项研究中，我们概述了一组公理，采取了一个步骤的PMD的功能定义，描述了一种改进的方法，可比较PMD检测样品之间具有显着不同的测序深度，并细化决策标准，样品是否包含PMD使用数据驱动的方法。将我们的方法应用于7个物种的267个甲基化组，我们证实了最近关于复制时间和PMD状态之间的一般关联的结果，并报告了在晚期复制域中识别出几个可重复的“逃逸”基因，这些基因逃脱了其直接基因组邻域的表达减少和低甲基化。我们还探索了人类和小鼠之间直系同源基因的不一致PMD状态，并观察到PMD状态与基因表达和局部基因密度的方向关联。我们改进的方法使低测序深度，群体水平的PMD变异研究成为可能，我们的结果进一步完善了PMD形成的模型，其中序列背景和区域表观基因组特征都在逐渐的全基因组低甲基化中发挥作用。
Partially methylated domains (PMDs) are a hallmark of epigenomes in reproducible and specific biological contexts, including cancer cells, the placenta, and cultured cell lines. Existing methods for deciding whether PMDs exist in a sample, as well as their identification, are few, often tailored to specific biological questions, and require high coverage samples for accurate identification. In this study, we outline a set of axioms that take a step towards a functional definition for PMDs, describe an improved method for comparable PMD detection across samples with substantially differing sequencing depths, and refine the decision criteria for whether a sample contains PMDs using a data-driven approach. Applying our method to 267 methylomes from 7 species, we corroborated recent results regarding the general association between replication timing and PMD state, and report identification of several reproducibly “escapee” genes within late-replicating domains that escape the reduced expression and hypomethylation of their immediate genomic neighborhood. We also explored the discordant PMD state of orthologous genes between human and mouse, and observed a directional association of PMD state with gene expression and local gene density. Our improved method makes low sequencing depth, population-level studies of PMD variation possible and our results further refine the model of PMD formation as one where sequence context and regional epigenomic features both play a role in gradual genome-wide hypomethylation.
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影响因子：
14.9
作者：
Burger L;Gaidatzis D;Schübeler D;Stadler MB
通讯作者：
Stadler MB
影响因子：
7
作者：
Hon, Gary C.;Hawkins, R. David;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
14.9
作者：
Karolchik, D;Hinrichs, AS;Kent, WJ
通讯作者：
Kent, WJ
DOI：
10.1073/pnas.1932072100
发表时间：
2003-09-30
影响因子：
11.1
作者：
Kent, WJ;Baertsch, R;Haussler, D
通讯作者：
Haussler, D
影响因子：
14.9
作者：
Hinrichs AS;Karolchik D;Baertsch R;Barber GP;Bejerano G;Clawson H;Diekhans M;Furey TS;Harte RA;Hsu F;Hillman-Jackson J;Kuhn RM;Pedersen JS;Pohl A;Raney BJ;Rosenbloom KR;Siepel A;Smith KE;Sugnet CW;Sultan-Qurraie A;Thomas DJ;Trumbower H;Weber RJ;Weirauch M;Zweig AS;Haussler D;Kent WJ
通讯作者：
Kent WJ