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PMID: 17603471 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.

Nature ·Vol. 448 ·No. 7153 ·2007-08-02 ·Pages 553-60

Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE

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.

MeSH Terms
Alleles Animals Cell Lineage/genetics Chromatin/genetics,metabolism CpG Islands/genetics Fibroblasts Gene Expression Regulation, Developmental Genome/genetics Genomic Imprinting Histones/metabolism Male Methylation Mice Pluripotent Stem Cells/cytology,metabolism Promoter Regions, Genetic/genetics Transcription, Genetic/genetics
Chemicals
Chromatin Histones
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Mikkelsen Tarjei S
Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
Ku Manching
Jaffe David B
Issac Biju
Lieberman Erez
Giannoukos Georgia
Alvarez Pablo
Brockman William
Kim Tae-Kyung
Koche Richard P
Lee William
Mendenhall Eric
O'Donovan Aisling
Presser Aviva
Russ Carsten
Xie Xiaohui
Meissner Alexander
Wernig Marius
Jaenisch Rudolf
Nusbaum Chad
Lander Eric S
Bernstein Bradley E
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature06008
Published
2007-08-02
Epub
2007-00-01
Pages
553-60
Language
English
Region
England
NLM ID
0410462
PMCID
PMC2921165
Subset
IM
Grants
NIGMS NIH HHS · R01 GM078986 · United States
NIGMS NIH HHS · R01 GM078986-01 · United States
NCI NIH HHS · T32 CA009216 · United States
Corrections
CommentIn
PMID: 17671496
External Links
PubMed source DOI: 10.1038/nature06008 PMC Full Text View journal details
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