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 Nusbaum, Eric S. Lander () and Bradley E. Bernstein ()
Additional contact information
Tarjei S. Mikkelsen: Broad Institute of Harvard and MIT,
Manching Ku: Broad Institute of Harvard and MIT,
David B. Jaffe: Broad Institute of Harvard and MIT,
Biju Issac: Broad Institute of Harvard and MIT,
Erez Lieberman: Broad Institute of Harvard and MIT,
Georgia Giannoukos: Broad Institute of Harvard and MIT,
Pablo Alvarez: Broad Institute of Harvard and MIT,
William Brockman: Broad Institute of Harvard and MIT,
Tae-Kyung Kim: Children’s Hospital, and
Richard P. Koche: Broad Institute of Harvard and MIT,
William Lee: Broad Institute of Harvard and MIT,
Eric Mendenhall: Broad Institute of Harvard and MIT,
Aisling O’Donovan: Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
Aviva Presser: Broad Institute of Harvard and MIT,
Carsten Russ: Broad Institute of Harvard and MIT,
Xiaohui Xie: Broad Institute of Harvard and MIT,
Alexander Meissner: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
Marius Wernig: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
Rudolf Jaenisch: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
Chad Nusbaum: Broad Institute of Harvard and MIT,
Eric S. Lander: Broad Institute of Harvard and MIT,
Bradley E. Bernstein: Broad Institute of Harvard and MIT,

Nature, 2007, vol. 448, issue 7153, 553-560

Abstract: 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.

Date: 2007
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DOI: 10.1038/nature06008

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