Zhou Wanding, Hinoue Toshinori, Barnes Bret, Mitchell Owen, Iqbal Waleed, Lee Sol Moe, Foy Kelly K, Lee Kwang-Ho, Moyer Ethan J, VanderArk Alexandra, Koeman Julie M, Ding Wubin, Kalkat Manpreet, Spix Nathan J, Eagleson Bryn, Pospisilik John Andrew, Szabó Piroska E, Bartolomei Marisa S, Vander Schaaf Nicole A, Kang Liang, Wiseman Ashley K, Jones Peter A, Krawczyk Connie M, Adams Marie, Porecha Rishi, Chen Brian H, Shen Hui, Laird Peter W
Center for Computational and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Genom. 2022 Jul 13;2(7). doi: 10.1016/j.xgen.2022.100144.
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. Notably, 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. 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.
我们开发了一种小鼠DNA甲基化芯片，其中包含296,070个探针，代表了小鼠DNA甲基化生物学的多样性。我们展示了一个小鼠甲基化图谱，作为一个丰富的参考资源，涵盖了1239个DNA样本，包括不同的组织、品系、年龄、性别和病理状态。我们描述了比较表观基因组学、基因组印记、表观遗传抑制剂、患者来源的异种移植物评估、回交追踪和表观遗传时钟的应用。我们剖析了与分化、衰老和肿瘤发生相关的DNA甲基化过程。值得注意的是，我们发现组织特异性甲基化特征定位于控制相应组织发育的转录因子的结合位点。与年龄相关的高甲基化在多梳抑制区域富集，而低甲基化在黏连蛋白复合体成员结合的区域增强。息肉相关的高甲基化影响调节肠道分化的增强子，而低甲基化靶向AP-1结合位点。这种Infinium小鼠甲基化微珠芯片（版本MM285）可供研究界广泛使用，并将加速在这个重要模式生物中进行的高样本通量研究。
