Landscape of monoallelic DNA accessibility in mouse embryonic stem cells and neural progenitor cells.
Nat Genet
; 49(3): 377-386, 2017 Mar.
Article
em En
| MEDLINE
| ID: mdl-28112738
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
DNA
/
Células-Tronco Neurais
/
Células-Tronco Embrionárias Murinas
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article