Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.
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.
Mikkelsen
Tarjei S
TS
Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
Ku
Manching
M
Jaffe
David B
DB
Issac
Biju
B
Lieberman
Erez
E
Giannoukos
Georgia
G
Alvarez
Pablo
P
Brockman
William
W
Kim
Tae-Kyung
TK
Koche
Richard P
RP
Lee
William
W
Mendenhall
Eric
E
O'Donovan
Aisling
A
Presser
Aviva
A
Russ
Carsten
C
Xie
Xiaohui
X
Meissner
Alexander
A
Wernig
Marius
M
Jaenisch
Rudolf
R
Nusbaum
Chad
C
Lander
Eric S
ES
Bernstein
Bradley E
BE
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
D002843:Chromatin; D006657:Histones