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Nature DOI:10.1038/nature06008

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

Publication TypeJournal Article
Year of Publication2007
AuthorsMikkelsen, TS, Ku, M, Jaffe, DB, Issac, B, Lieberman, E, Giannoukos, G, Alvarez, P, Brockman, W, Kim, T-K, 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
Date Published2007 Aug 02
KeywordsAlleles, Animals, Cell Lineage, Chromatin, CpG Islands, Fibroblasts, Gene Expression Regulation, Developmental, Genome, Genomic Imprinting, Histones, Male, Methylation, Mice, Pluripotent Stem Cells, Promoter Regions, Genetic, Transcription, Genetic

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.


Alternate JournalNature
PubMed ID17603471
PubMed Central IDPMC2921165
Grant ListR01 GM078986 / GM / NIGMS NIH HHS / United States
R01 GM078986-01 / GM / NIGMS NIH HHS / United States
T32 CA009216 / CA / NCI NIH HHS / United States