Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci.
Science
; 361(6409)2018 09 28.
Article
in En
| MEDLINE
| ID: mdl-30139913
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genome, Human
/
Disease
/
DNA Methylation
/
Polymorphism, Single Nucleotide
/
Allelic Imbalance
/
Epigenesis, Genetic
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Science
Year:
2018
Document type:
Article
Affiliation country:
United States