title: Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.
abstract: We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
authors.forename: Tarjei S
authors.initials: TS
authors.lastname: Mikkelsen
authors.forename: Manching
authors.initials: M
authors.lastname: Ku
authors.forename: David B
authors.initials: DB
authors.lastname: Jaffe
authors.forename: Biju
authors.initials: B
authors.lastname: Issac
authors.forename: Erez
authors.initials: E
authors.lastname: Lieberman
authors.forename: Georgia
authors.initials: G
authors.lastname: Giannoukos
authors.forename: Pablo
authors.initials: P
authors.lastname: Alvarez
authors.forename: William
authors.initials: W
authors.lastname: Brockman
authors.forename: Tae-Kyung
authors.initials: TK
authors.lastname: Kim
authors.forename: Richard P
authors.initials: RP
authors.lastname: Koche
authors.forename: William
authors.initials: W
authors.lastname: Lee
authors.forename: Eric
authors.initials: E
authors.lastname: Mendenhall
authors.forename: Aisling
authors.initials: A
authors.lastname: O'Donovan
authors.forename: Aviva
authors.initials: A
authors.lastname: Presser
authors.forename: Carsten
authors.initials: C
authors.lastname: Russ
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xie
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
authors.forename: Marius
authors.initials: M
authors.lastname: Wernig
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.forename: Chad
authors.initials: C
authors.lastname: Nusbaum
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Bernstein
mesh_terms: D000483:Alleles; D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics; D005347:Fibroblasts; D018507:Gene Expression Regulation, Developmental; D016678:Genome / Q000235:genetics*; D018392:Genomic Imprinting; D006657:Histones / Q000378:metabolism; D008297:Male; D008745:Methylation; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones