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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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Cites
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
Self-citationThe Role of Chromatin during Transcription
Li, B., Carey, M., & Workman, J. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.015 · Cited by 3,503
The Transcriptional Landscape of the Mammalian Genome
Carninci, P., Kasukawa, T., Katayama, S., Gough, J., Frith, M. C., Maeda, N., Oyama, R., Ravasi, T., Lenhard, B., Wells, C. A., et al. (2005) · Science · doi:10.1126/science.1112014 · Cited by 3,492
Polycomb complexes repress developmental regulators in murine embryonic stem cells
Boyer, L. A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L. A., Lee, T. I., Levine, S. S., Wernig, M., Tajonar, A., Ray, M. K., et al. (2006) · Nature · doi:10.1038/nature04733 · Cited by 2,568
Self-citationGenomic DNA methylation: the mark and its mediators.
Klose, R. J., & Bird, A. P. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.12.008 · Cited by 2,501
Weber, M., Hellmann, I., Stadler, M. B., Ramos, L., Pääbo, S., Rebhan, M., & Schübeler, D. (2007) · Nature Genetics · doi:10.1038/ng1990 · Cited by 2,297
Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells
Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Levine, S. S., Kumar, R., Chevalier, B. S., Johnstone, S. E., Cole, M. F., Isono, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.043 · Cited by 2,296
Self-citationBernstein, B. E., Meissner, A., & Lander, E. S. (2007) · Cell · doi:10.1016/j.cell.2007.01.033 · Cited by 2,086
Self-citationGeneration and initial analysis of more than 15,000 full-length human and mouse cDNA sequences
Mammalian Gene Collection (MGC) Program Team* (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242603899 · Cited by 1,756
Genomic Maps and Comparative Analysis of Histone Modifications in Human and Mouse
Bernstein, B., Kamal, M., Lindblad‐Toh, K., Bekiranov, S., Bailey, D. K., Huebert, D. J., McMahon, S., Karlsson, E. K., Kulbokas, E. J., Gingeras, T., et al. (2005) · Cell · doi:10.1016/j.cell.2005.01.001 · Cited by 1,567
Self-citationGenome Regulation by Polycomb and Trithorax Proteins
Schuettengruber, B., Chourrout, D., Vervoort, M., Leblanc, B., & Cavalli, G. (2007) · Cell · doi:10.1016/j.cell.2007.02.009 · Cited by 1,418
Saxonov, S., Berg, P., & Brutlag, D. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510310103 · Cited by 1,401
Chromatin signatures of pluripotent cell lines
Azuara, V., Perry, P., Sauer, S., Spivakov, M., Jørgensen, H. F., John, R. M., Gouti, M., Casanova, M., Warnes, G., Merkenschlager, M., et al. (2006) · Nature Cell Biology · doi:10.1038/ncb1403 · Cited by 1,357
Epigenetic Regulation of Cellular Memory by the Polycomb and Trithorax Group Proteins
Ringrose, L., & Paro, R. (2004) · Annual Review of Genetics · doi:10.1146/annurev.genet.38.072902.091907 · Cited by 1,093
Hutchinson, J. N., Ensminger, A. W., Clemson, C., Lynch, C. R., Lawrence, J. B., & Chess, A. J. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-39 · Cited by 1,017
A high-resolution map of active promoters in the human genome
Kim, T. H., Barrera, L. O., Zheng, M., Qu, C., Singer, M. A., Richmond, T., Wu, Y., Green, R. D., & Ren, B. (2005) · Nature · doi:10.1038/nature03877 · Cited by 954
Self-citationNiche-Independent Symmetrical Self-Renewal of a Mammalian Tissue Stem Cell
Conti, L., Pollard, S. M., Gorba, T., Reitano, E., Toselli, M., Biella, G. R., Sun, Y., Sanzone, S., Ying, Q., Cattaneo, E. F., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030283 · Cited by 876
Transcription and Processing of Human microRNA Precursors
Cullen, B. R. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.12.002 · Cited by 774
The glial identity of neural stem cells
Doetsch, F. (2003) · Nature Neuroscience · doi:10.1038/nn1144 · Cited by 724
The Polycomb Group Protein Suz12 Is Required for Embryonic Stem Cell Differentiation
Pasini, D., Bracken, A. P., Hansen, J. B., Capillo, M., & Helin, K. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01432-06 · Cited by 714
The profile of repeat‐associated histone lysine methylation states in the mouse epigenome
Martens, J. H. A., O’Sullivan, R. J., Braunschweig, U., Opravil, S., Radolf, M., Steinlein, P., & Jenuwein, T. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600545 · Cited by 697
Specific microRNAs modulate embryonic stem cell-derived neurogenesis.
Krichevsky, A. M., Sonntag, K.-C., Isacson, O., & Kosik, K. S. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0441 · Cited by 692
Genetic and Epigenetic Regulators of Pluripotency
Surani, M. A., Hayashi, K., & Hájková, P. (2007) · Cell · doi:10.1016/j.cell.2007.02.010 · Cited by 676
Buck, M. J., & Lieb, J. D. (2004) · Genomics · doi:10.1016/j.ygeno.2003.11.004 · Cited by 613
Mutations in SOX2 cause anophthalmia
Fantes, J. A., Ragge, N., Lynch, S. A., McGill, N. I., Collin, J. R. O., Howard‐Peebles, P. N., Hayward, C., Vivian, A. J., Williamson, K. A., van Heyningen, V., et al. (2003) · Nature Genetics · doi:10.1038/ng1120 · Cited by 538
A Large Imprinted microRNA Gene Cluster at the Mouse Dlk1-Gtl2 Domain
Seitz, H., Royo, H., Bortolin, M.-L., Lin, S.-P., Ferguson-Smith, A. C., & Cavaillé, J. (2004) · Genome Research · doi:10.1101/gr.2743304 · Cited by 515
Active chromatin domains are defined by acetylation islands revealed by genome-wide mappingPreprint
Roh, T., Cuddapah, S., & Zhao, K. (2005) · Genes & Development · doi:10.1101/gad.1272505 · Cited by 469
Spatial Distribution of Di- and Tri-methyl Lysine 36 of Histone H3 at Active Genes
Bannister, A. J., Schneider, R., Myers, F. A., Thorne, A. W., Crane‐Robinson, C., & Kouzarides, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500796200 · Cited by 459
Noncoding RNAs and Gene Silencing
Zaratiegui, M., Irvine, D. V., & Martienssen, R. A. (2007) · Cell · doi:10.1016/j.cell.2007.02.016 · Cited by 438
Profile of Histone Lysine Methylation across Transcribed Mammalian Chromatin
Vakoc, C. R., Sachdeva, M. M., Wang, H., & Blobel, G. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01529-06 · Cited by 427
Mechanisms regulating imprinted genes in clusters
Edwards, C. A., & Ferguson‐Smith, A. C. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.04.013 · Cited by 422
Applications of DNA tiling arrays for whole-genome analysis
Mockler, T. C., & Ecker, J. R. (2004) · Genomics · doi:10.1016/j.ygeno.2004.10.005 · Cited by 404
Suz12 binds to silenced regions of the genome in a cell-type-specific mannerPreprint
Squazzo, S. L., O’Geen, H., Komashko, V., Krig, S. R., Jin, V. X., Jang, S.-W., Margueron, R., Reinberg, D., Green, R., & Farnham, P. (2006) · Genome Research · doi:10.1101/gr.5306606 · Cited by 324
Antisense Transcription and Heterochromatin at the DM1 CTG Repeats Are Constrained by CTCF
Cho, D. H., Thienes, C. P., Mahoney, S. E., Analau, E., Filippova, G. N., & Tapscott, S. J. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.09.002 · Cited by 283
Convergent evolution of genomic imprinting in plants and mammals
Feil, R., & Berger, F. (2007) · Trends in Genetics · doi:10.1016/j.tig.2007.02.004 · Cited by 277
Service, R. F. (2006) · Science · doi:10.1126/science.311.5767.1544 · Cited by 269
RNAi and expression of retrotransposons MuERV-L and IAP in preimplantation mouse embryos
Svoboda, P., Stein, P., Anger, M., Bernstein, E., Hannon, G. J., & Schultz, R. M. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.01.028 · Cited by 218
Differential histone modifications mark mouse imprinting control regions during spermatogenesis
Delaval, K., Govin, J., Cerqueira, F., Rousseaux, S., Khochbin, S., & Feil, R. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601513 · Cited by 218
Alexander, D. L., Ganem, L. G., Fernández‐Salguero, P. M., Gonzalez, F. J., & Jefcoate, C. R. E. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.22.3311 · Cited by 201
Wang, X., Su, H., & Bradley, A. (2002) · Genes & Development · doi:10.1101/gad.1004802 · Cited by 183
Rao, B., Shibata, Y., Strahl, B. D., & Lieb, J. D. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9447-9459.2005 · Cited by 178
Garreta, E., Genové, E., Borrós, S., & Semino, C. E. (2006) · Tissue Engineering · doi:10.1089/ten.2006.12.2215 · Cited by 158
RNAi‐directed assembly of heterochromatin in fission yeast
Verdel, A., & Moazed, D. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.08.083 · Cited by 152
Kim, A., Kiefer, C. M., & Dean, A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01684-06 · Cited by 96
Primary mouse embryonic fibroblasts: A model of mesenchymal cartilage formation
Lengner, C. J., Lepper, C., van Wijnen, A. J., Stein, J. L., Stein, G. S., & Lian, J. B. (2004) · Journal of Cellular Physiology · doi:10.1002/jcp.20118 · Cited by 86
Baust, C., Gagnier, L., Baillie, G. J., Harris, M. J., Juriloff, D. M., & Mager, D. L. (2003) · Journal of Virology · doi:10.1128/jvi.77.21.11448-11458.2003 · Cited by 60
The Human β-Globin Locus Control Region Can Silence as Well as Activate Gene Expression
Feng, Y., Warin, R., Li, T., Olivier, E. N., Besse, A., Lobell, A., Fu, H., Lin, C. M., Aladjem, M. I., & Bouhassira, E. E. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.10.3864-3874.2005 · Cited by 34
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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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