title: Landscape of monoallelic DNA accessibility in mouse embryonic stem cells and neural progenitor cells.
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 F1system, 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.
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Ava C
authors.initials: AC
authors.lastname: Carter
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
authors.forename: Anne-Valerie
authors.initials: AV
authors.lastname: Gendrel
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: Attia
authors.affiliation: Data Sciences and Statistics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Loftus
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.|Departement of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenleaf
authors.affiliation: Data Sciences and Statistics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Tibshirani
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000483:Alleles; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002843:Chromatin / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D008297:Male; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*
chemical_list: D002843:Chromatin; D004247:DNA