Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci
Name
nihms-990272.pdf
Description
Accepted version
Size
1.11 MB
Format
Adobe PDF
Checksum (MD5)
516571ffe9cf3c794307dc213e61cc0c
Author(s)
Altshuler, Robert Charles
Onuchic, Vitor
Lurie, Eugene
Carrero, Ivenise
Pawliczek, Piotr
Patel, Ronak Y.
Rozowsky, Joel
Galeev, Timur
Huang, Zhuoyi
Harris, R. Alan
Date Issued
September 2018
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Onuchic, Vitor et al. "Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci." Science 361, 6409 (September 2018): eaar3146 © American Association for the Advancement of Science
Version
Author's final manuscript
Abstract
To assess the impact of genetic variation in regulatory loci on human health, we constructed a high-resolution map of allelic imbalances in DNA methylation, histone marks, and gene transcription in 71 epigenomes from 36 distinct cell and tissue types from 13 donors. Deep whole-genome bisulfite sequencing of 49 methylomes revealed sequence-dependent CpG methylation imbalances at thousands of heterozygous regulatory loci. Such loci are enriched for stochastic switching, which is defined as random transitions between fully methylated and unmethylated states of DNA.The methylation imbalances at thousands of loci are explainable by different relative frequencies of the methylated and unmethylated states for the two alleles. Further analyses provided a unifying model that links sequence-dependent allelic imbalances of the epigenome, stochastic switching at gene regulatory loci, and disease-associated genetic variation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1126/SCIENCE.AAR3146
