Mouse DNA methylation atlas using Infinium Mouse Methylation Beadchips. Mouse DNA methylation atlas using Infinium Mouse Methylation Beadchips

Design, annotation, and technical and biological validation of the MouseMethylation Beadchips (MM285) platform. Application of the mouse array for tissue and tumor epigenetics, comparative epigenomics, genomic imprinting, epigenetic inhibitors, PDX assessment, backcross tracing, and epigenetic clocks. Overall design: 1239 DNA samples encompassing distinct tissues, strains, age, sex, and pathologies. We have developed a mouse DNA methylation array that contains 296,070 probes representing the diversity of mouse DNA methylation biology. We present a mouse methylation atlas as a rich reference resource of 1,239 DNA samples encompassing distinct tissues, strains, ages, sexes, and pathologies. We describe applications for comparative epigenomics, genomic imprinting, epigenetic inhibitors, patient-derived xenograft assessment, backcross tracing, and epigenetic clocks. We dissect DNA methylation processes associated with differentiation, aging, and tumorigenesis. We find that tissue-specific methylation signatures localize to binding sites for transcription factors controlling the corresponding tissue development. Age-associated hypermethylation is enriched at regions of Polycomb repression, while hypomethylation is enhanced at regions bound by cohesin complex members. ApcMin/+ polyp-associated hypermethylation affects enhancers regulating intestinal differentiation, while hypomethylation targets AP-1 binding sites. This Infinium Mouse Methylation BeadChip (version MM285) is widely accessible to the research community and will accelerate high-sample-throughput studies in this important model organism. More probe annotations can be found at http://zwdzwd.github.io/InfiniumAnnotation#mouse More sample information can be found at https://github.com/zhou-lab/2022MM285CellGenomics

小鼠甲基化芯片（MouseMethylation Beadchips, MM285）平台的设计、注释及技术与生物学验证。该小鼠甲基化芯片可应用于组织与肿瘤表观遗传学、比较表观基因组学、基因组印记、表观遗传抑制剂、患者来源异种移植（Patient-Derived Xenograft, PDX）评估、回交追踪以及表观遗传时钟研究。整体设计：涵盖不同组织、品系、年龄、性别与病理状态的1239份DNA样本。
本研究开发了一款包含296070个探针的小鼠DNA甲基化芯片，可覆盖小鼠DNA甲基化生物学的全部多样性。我们构建了小鼠甲基化图谱，其作为丰富的参考资源，涵盖1239份来自不同组织、品系、年龄、性别及病理状态的DNA样本。本研究阐述了该芯片在比较表观基因组学、基因组印记、表观遗传抑制剂、PDX评估、回交追踪以及表观遗传时钟领域的应用。我们解析了与细胞分化、衰老及肿瘤发生相关的DNA甲基化调控过程。研究发现，组织特异性甲基化特征富集于调控对应组织发育的转录因子结合位点。与年龄相关的高甲基化富集于多梳蛋白（Polycomb）抑制区域，而低甲基化则富集于黏连蛋白复合体亚基结合的区域。ApcMin/+息肉相关的高甲基化会调控肠道分化相关增强子区域，而低甲基化则靶向结合激活蛋白1（AP-1）的结合位点。这款Infinium小鼠甲基化芯片（版本号MM285）可被科研社区广泛获取，将助力这一重要模式生物的大样本高通量研究。更多探针注释信息可访问 http://zwdzwd.github.io/InfiniumAnnotation#mouse，更多样本相关信息可访问 https://github.com/zhou-lab/2022MM285CellGenomics