Work

Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci

Year: 2018

Type: article

Study design: Observational Study

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.

Source: Science

DOI: 10.1126/science.aar3146

Authors: Vitor Onuchic, Eugene Lurie, Ivenise Carrero, Piotr Pawliczek, Ronak Y. Patel, Joel Rozowsky, Timur Galeev, Zhuoyi Huang, Robert C. Altshuler, Zhizhuo Zhang, R. Alan Harris, Cristian Coarfa, Lillian Ashmore, Jessica W. Bertol, Walid D. Fakhouri, Fuli Yu, Manolis Kellis, Mark Gerstein, Aleksandar Milosavljevic

Institutions: Baylor College of Medicine, Yale University, Broad Institute, Harvard University, MIT Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, The University of Texas Health Science Center at Houston

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Institute of General Medical Sciences, U.S. National Library of Medicine

Awards: Epigenomic variation atlas across human tissues and individuals in GTEx, G1623857992, Epigenomics Data Analysis and Coordination Center at Baylor College of Medicine, Modeling of pathological significance of non-coding DNA variants in cis-overlapping motifs of p53 and cMyc, Interpreting non-coding variants using epigenomics, regulatory models, & validation experiments, G4590432111, Network-based prediction and validation of causal schizophrenia genes and variants, Program in Human and Molecular Genetics, Comparative analysis and regulatory architecture of epigenomics datasets, Powering whole genome sequence-based genetic discovery for common human diseases, EDAC: ENCODE Data Analysis Center, G8773276167, NLM Research Training Program in Biomedical Informatics and Data Science for Predoctoral and Postdoctoral Fellows

OpenAlex ID: W2888526621

FWCI: 4.89

Cites: 78

Cited by: 107

Related to: 10