DNA methylation dynamics and dysregulation delineated by high-throughput profiling in the mouse.

Autor: Zhou 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., Hinoue T; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Barnes B; Illumina, Inc., Bioinformatics and Instrument Software Department, San Diego, CA 92122, USA., Mitchell O; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Iqbal W; Center for Computational and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., Lee SM; Center for Computational and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., Foy KK; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Lee KH; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Moyer EJ; Center for Computational and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., VanderArk A; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI 49503, USA., Koeman JM; Genomics Core, Van Andel Institute, Grand Rapids, MI 49503, USA., Ding W; Center for Computational and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., Kalkat M; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Spix NJ; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Eagleson B; Vivarium and Transgenics Core, Van Andel Institute, Grand Rapids, MI 49503, USA., Pospisilik JA; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Szabó PE; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Bartolomei MS; Department of Cell and Developmental Biology, Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Vander Schaaf NA; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.; Present address: Department of Biological Sciences, Olivet Nazarene University, Bourbonnais, IL 60914, USA., Kang L; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Wiseman AK; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Jones PA; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Krawczyk CM; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI 49503, USA., Adams M; Genomics Core, Van Andel Institute, Grand Rapids, MI 49503, USA., Porecha R; Illumina, Inc., Bioinformatics and Instrument Software Department, San Diego, CA 92122, USA., Chen BH; FOXO Technologies Inc., Minneapolis, MN 55402, USA., Shen H; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Laird PW; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.; Lead contact.
Jazyk: angličtina
Zdroj: Cell genomics [Cell Genom] 2022 Jul 13; Vol. 2 (7).
DOI: 10.1016/j.xgen.2022.100144
Abstrakt: 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. Apc Min /+ 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.
Databáze: MEDLINE