Journal article
DNA methylation dynamics and dysregulation delineated by high-throughput profiling in the mouse
Cell genomics, v 2(7), 100144
13 Jul 2022
PMID: 35873672
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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. 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.
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•Design, annotation, and validation of the Infinium Mouse DNA Methylation BeadChip•Mouse methylome atlas of 1,239 diverse cell types, strains, ages, and pathologies•Bioinformatics for tissues, imprinting, comparative epigenomics, strain SNPs, and PDXs•Tumor- and age-associated DNA methylation dynamics and an epigenetic clock
Infinium arrays are a cost-effective high-throughput DNA methylation profiling tool for human samples. Zhou et al. have developed an equivalent array for the mouse and used it to generate a DNA methylome atlas representing the diversity of DNA methylation biology in development, aging, and disease in this important model organism.
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Details
- Title
- DNA methylation dynamics and dysregulation delineated by high-throughput profiling in the mouse
- Creators
- Wanding Zhou - University of PennsylvaniaToshinori Hinoue - Van Andel InstituteBret Barnes - IlluminaOwen Mitchell - Van Andel InstituteWaleed Iqbal - Children's Hospital of PhiladelphiaSol Moe Lee - Children's Hospital of PhiladelphiaKelly K. Foy - Van Andel InstituteKwang-Ho Lee - Van Andel InstituteEthan J. Moyer - Children's Hospital of PhiladelphiaAlexandra VanderArk - Van Andel InstituteJulie M. Koeman - Van Andel InstituteWubin Ding - Children's Hospital of PhiladelphiaManpreet Kalkat - Van Andel InstituteNathan J. Spix - Van Andel InstituteBryn Eagleson - Van Andel InstituteJohn Andrew Pospisilik - Van Andel InstitutePiroska E. Szabó - Van Andel InstituteMarisa S. Bartolomei - University of PennsylvaniaNicole A. Vander Schaaf - Van Andel InstituteLiang Kang - Van Andel InstituteAshley K. Wiseman - Van Andel InstitutePeter A. Jones - Van Andel InstituteConnie M. Krawczyk - Van Andel InstituteMarie Adams - Van Andel InstituteRishi Porecha - Illumina, Inc., Bioinformatics and Instrument Software Department, San Diego, CA 92122, USABrian H. Chen - FOXO Technologies Inc., Minneapolis, MN 55402, USAHui Shen - Van Andel InstitutePeter W. Laird - Van Andel Institute
- Publication Details
- Cell genomics, v 2(7), 100144
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:001104053200005
- Scopus ID
- 2-s2.0-85129890920
- Other Identifier
- 991022083951304721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Genetics & Heredity