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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Open accessAbstract
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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“Useful tools will include maps of evolutionary conservation (108) and chromatin state (140), as well as databases of cell-state signatures, such as genome-wide expression patterns, that may integrate aspects of cell biology under resting and provoked conditions (141).”
From Genetic Mapping in Human Disease (2008) · cites this paper as [140]
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“Intriguingly, we also observed increased levels of both H3K18ac and H3K18cr at bivalent genes (Fig. 5B), that is, poised genes marked with both H3K4me3 and H3K27me3 in ES cells35,36, suggesting a role for HDAC1/2 in controlling the activity of developmentally regulated genes prior to ES cell differentiation.”
From Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo (2018) · cites this paper as [36]
In the citing paper
“Intriguingly, we also observed increased levels of both H3K18ac and H3K18cr at bivalent genes (Fig. 5B), that is, poised genes marked with both H3K4me3 and H3K27me3 in ES cells35,36, suggesting a role for HDAC1/2 in controlling the activity of developmentally regulated genes prior to ES cell differentiation.”
From Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo (2018) · cites this paper as [36]
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Metadata
- 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
- Venue
- Nature
- Published
- 2007-07-01
- Volume
- 448
- Issue
- 7153
- Pages
- 553-560
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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