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Nat Genet. 2017 Mar;49(3):377-386. doi: 10.1038/ng.3769. Epub 2017 Jan 23.

Landscape of monoallelic DNA accessibility in mouse embryonic stem cells and neural progenitor cells.

Author information

1
Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
2
Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
3
Data Sciences and Statistics, Stanford University School of Medicine, Stanford, California, USA.
4
Departement of Genetics, Stanford University School of Medicine, Stanford, California, USA.

Abstract

We developed an allele-specific assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to genotype and profile active regulatory DNA across the genome. Using a mouse hybrid F1 system, we found that monoallelic DNA accessibility across autosomes was pervasive, developmentally programmed and composed of several patterns. Genetically determined accessibility was enriched at distal enhancers, but random monoallelically accessible (RAMA) elements were enriched at promoters and may act as gatekeepers of monoallelic mRNA expression. Allelic choice at RAMA elements was stable across cell generations and bookmarked through mitosis. RAMA elements in neural progenitor cells were biallelically accessible in embryonic stem cells but premarked with bivalent histone modifications; one allele was silenced during differentiation. Quantitative analysis indicated that allelic choice at the majority of RAMA elements is consistent with a stochastic process; however, up to 30% of RAMA elements may deviate from the expected pattern, suggesting a regulated or counting mechanism.

PMID:
28112738
PMCID:
PMC5357084
DOI:
10.1038/ng.3769
[Indexed for MEDLINE]
Free PMC Article

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