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

Tarjei S. Mikkelsen, Manching Ku, David B. Jaffe, Biju Issac, Erez Lieberman, Georgia Giannoukos, Pablo Alvarez, William Brockman, Tae Kyung Kim, Richard P. Koche, William Lee, Eric Mendenhall, Aisling O'Donovan, Aviva Presser, Carsten Russ, Xiaohui Xie, Alexander Meissner, Marius Wernig, Rudolf Jaenisch, Chad NusbaumEric S. Lander, Bradley E. Bernstein

Research output: Contribution to journalArticle

2899 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)553-560
Number of pages8
JournalNature
Volume448
Issue number7153
DOIs
StatePublished - Aug 2 2007

ASJC Scopus subject areas

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    Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T. K., Koche, R. P., Lee, W., Mendenhall, E., O'Donovan, A., Presser, A., Russ, C., Xie, X., Meissner, A., Wernig, M., Jaenisch, R., ... Bernstein, B. E. (2007). Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature, 448(7153), 553-560. https://doi.org/10.1038/nature06008