Cited by 4,129Genomics and Chromatin DynamicsEpigenetics and DNA MethylationChromatin Remodeling and Cancer

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

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Mikkelsen, Tarjei S., 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.·2007·Nature

DOI 10.1038/nature06008PMC PMC2921165

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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.

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Authors: 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., Nusbaum, C., Lander, E. S., & Bernstein, B. E.
Affiliations: Broad Institute (US)
Children's Hospital (TN)
Massachusetts General Hospital (US)
Whitehead Institute for Biomedical Research (US)
Corresponding author: Lander, Eric S.
Bernstein, Bradley E.
ORCID: Mikkelsen, Tarjei S.
Ku, Manching
Jaffe, David B.
Issac, Biju
Alvarez, Pablo
Kim, Tae-Kyung
Koche, Richard P.
Lee, William
Mendenhall, Eric
Xie, Xiaohui
Meissner, Alexander
Wernig, Marius
Jaenisch, Rudolf
Nusbaum, Chad
Lander, Eric S.
Bernstein, Bradley E.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2007-07-01
Volume: 448
Issue: 7153
Pages: 553-560
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature06008
PMC: PMC2921165
OpenAlex: W2017840637
Cited by: 4,129
References: 48
Citations by year: 2026: 58 · 2025: 78 · 2024: 106 · 2023: 116 · 2022: 144 · 2021: 200 · 2020: 127 · 2019: 185 · 2018: 163 · 2017: 200 · 2016: 210 · 2015: 277 · 2014: 291 · 2013: 340 · 2012: 364
FWCI: 122.52
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
Funders: National Cancer Institute (T32CA009216)
National Institute of General Medical Sciences (R01GM078986)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: histone modifications, chromatin state, histone trimethylation, H3K4 trimethylation, H3K27me3, H3K36 trimethylation, H3K9 trimethylation, mouse embryonic stem cells, neural progenitor cells, embryonic fibroblasts, gene expression, gene repression, imprinting control regions, long terminal repeat, satellite DNA, telomeres, single nucleotide polymorphisms, ChIP-seq, pluripotency, lineage commitment
MeSH terms: Alleles, Animals, Chromatin, Fibroblasts, Histones, Male, Methylation, Promoter Regions, Genetic, Transcription, Genetic, Genome, Genomic Imprinting, Gene Expression Regulation, Developmental, CpG Islands, Cell Lineage, Pluripotent Stem Cells, Mice

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

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