Genome-scale DNA methylation maps of pluripotent and differentiated cells
Open accessAbstract
DNA methylation is essential for normal development and has been implicated in many pathologies including cancer. Our knowledge about the genome-wide distribution of DNA methylation, how it changes during cellular differentiation and how it relates to histone methylation and other chromatin modifications in mammals remains limited. Here we report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput reduced representation bisulphite sequencing and single-molecule-based sequencing, we generated DNA methylation maps covering most CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for mouse embryonic stem cells, embryonic-stem-cell-derived and primary neural cells, and eight other primary tissues. Several key findings emerge from the data. First, DNA methylation patterns are better correlated with histone methylation patterns than with the underlying genome sequence context. Second, methylation of CpGs are dynamic epigenetic marks that undergo extensive changes during cellular differentiation, particularly in regulatory regions outside of core promoters. Third, analysis of embryonic-stem-cell-derived and primary cells reveals that 'weak' CpG islands associated with a specific set of developmentally regulated genes undergo aberrant hypermethylation during extended proliferation in vitro, in a pattern reminiscent of that reported in some primary tumours. More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine.
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Sequencing-based techniques provide better genomic coverage than the 450K array and can assess genetic variants and allele-specific methylation beyond preselected microarray probes.
“They provide better genomic coverage than 450K array, and can assess the genetic variants and allele-specific methylation beyond the preselected microarray probes.”
From Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases (2016) · cites this paper as Meissner et al., 2008
DNA methylation is thought to be involved in disease pathology through its influence on gene expression and cellular function.
“DNA methylation is thought to be involved in disease pathology through its influence on gene expression and cellular function5,6.”
From Methylome-wide change associated with response to electroconvulsive therapy in depressed patients (2021) · cites this paper as [6]
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DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124 · see citing works
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 · see citing works
Self-citationJones, P. A., & Baylin, S. B. (2007) · Cell · doi:10.1016/j.cell.2007.01.029 · Cited by 4,515 · see citing works
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129 · see citing works
Self-citationHeintzman, N. D., Stuart, R. K., Hon, G., Fu, Y., Ching, C. W., Hawkins, R. D., Barrera, L. O., Van Calcar, S., Qu, C., Ching, K. A., et al. (2007) · Nature Genetics · doi:10.1038/ng1966 · Cited by 3,398 · see citing works
Frommer, M., McDonald, L. E., Millar, D. S., Collis, C. M., Watt, F., Grigg, G. W., Molloy, P. L., & Paul, C. L. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.5.1827 · Cited by 3,238 · see citing works
Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning
Cokus, S. J., Feng, S.-H., Zhang, X.-Y., Chen, Z., Merriman, B., Haudenschild, C., Pradhan, S., Nelson, S., Pellegrini, M., & Jacobsen, S. (2008) · Nature · doi:10.1038/nature06745 · Cited by 2,278 · see citing works
Self-citationWeber, M., Hellmann, I., Stadler, M. B., Ramos, L., Pääbo, S., Rebhan, M., & Schübeler, D. (2007) · Nature Genetics · doi:10.1038/ng1990 · Cited by 2,267 · see citing works
The DNA methyltransferases of mammals
Bestor, T. H. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.16.2395 · Cited by 2,045 · see citing works
Stability and flexibility of epigenetic gene regulation in mammalian development
Reik, W. (2007) · Nature · doi:10.1038/nature05918 · Cited by 1,963 · see citing works
DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA
Ooi, S. K. T., Qiu, C., Bernstein, E., Li, K., Jia, D., Yang, Z., Erdjument‐Bromage, H., Tempst, P., Lin, S., Allis, C. D., et al. (2007) · Nature · doi:10.1038/nature05987 · Cited by 1,558 · see citing works
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 1,509 · see citing works
Self-citationSaxonov, S., Berg, P., & Brutlag, D. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510310103 · Cited by 1,401 · see citing works
DNA methylation profiling of human chromosomes 6, 20 and 22
Eckhardt, F., Lewin, J., Cortese, R., Rakyan, V. K., Attwood, J., Burger, M., Burton, J. H., Cox, T. V., Davies, R., Down, T. A., et al. (2006) · Nature Genetics · doi:10.1038/ng1909 · Cited by 1,350 · see citing works
Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis
Meissner, A. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki901 · Cited by 1,203 · see citing works
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 857 · see citing works
An SNP map of the human genome generated by reduced representation shotgun sequencing
Altshuler, D., Pollara, V. J., Cowles, C. R., Etten, W. J. V., Baldwin, J., Linton, L., & Lander, E. S. (2000) · Nature · doi:10.1038/35035083 · Cited by 725 · see citing works
Self-citationA Novel CpG Island Set Identifies Tissue-Specific Methylation at Developmental Gene Loci
Illingworth, R. S., Kerr, A. R. W., DeSousa, D., Jørgensen, H. F., Ellis, P., Stalker, J., Jackson, D. K., Clee, C. M., Plumb, R. W., Rogers, J., et al. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060022 · Cited by 637 · see citing works
Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replicationPreprint
Estève, P., Chin, H. G., Smallwood, A., Feehery, G. R., Gangisetty, O., Karpf, A. R., Carey, M., & Pradhan, S. (2006) · Genes & Development · doi:10.1101/gad.1463706 · Cited by 539 · see citing works
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 406 · see citing works
The epigenetics of cancer etiology
Feinberg, A. P. (2004) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2004.06.005 · Cited by 336 · see citing works
Remote control of gene transcription
West, A. G., & Fraser, P. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi104 · Cited by 302 · see citing works
Aubert, J., Stavridis, M. P., Tweedie, S., O’Reilly, M., Vierlinger, K., Li, M., Ghazal, P., Pratt, T., Mason, J. O., Roy, D. J., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1734197100 · Cited by 248 · see citing works
Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies
Smiraglia, D. J. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.13.1413 · Cited by 243 · see citing works
Voo, K. S., Carlone, D. L., Jacobsen, B. M., Flodin, A., & Skalnik, D. G. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.6.2108-2121.2000 · Cited by 194 · see citing works
Distinct Genetic Signatures among Pilocytic Astrocytomas Relate to Their Brain Region Origin
Sharma, M. K., Mansur, D. B., Reifenberger, G., Perry, A., Leonard, J. R., Aldape, K., Albin, M. G., Emnett, R. J., Loeser, S., Watson, M. A., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-0973 · Cited by 175 · see citing works
Stem Cell Chromatin Patterns: An Instructive Mechanism for DNA Hypermethylation?
Ohm, J. E., & Baylin, S. B. (2007) · Cell Cycle · doi:10.4161/cc.6.9.4210 · Cited by 102 · see citing works
Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells
Shen, Y., Chow, J., Wang, Z., & Fan, G. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl188 · Cited by 79 · see citing works
Embryonic Stem Cell‐Derived Neural Progenitors Display Temporal Restriction to Neural Patterning
Bouhon, I. A., Joannides, A. J., Kato, H., Chandran, S., & Allen, N. D. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0031 · Cited by 54 · see citing works
Methylation and expression of the Myo D1 determination gene
Jones, P. A., Wolkowicz, M. J., Harrington, M. A., & Gonzales, F. A. (1990) · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · doi:10.1098/rstb.1990.0011 · Cited by 32 · see citing works
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An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072 · see citing works
Self-citationHeinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382 · see citing works
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,949 · see citing works
Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368 · see citing works
Self-citationDNA methylation and its basic function
Moore, L. D., Le, T., & Fan, G. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.112 · Cited by 4,906 · see citing works
Human DNA methylomes at base resolution show widespread epigenomic differences
Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., Nery, J. R., Lee, L., Ye, Z., Ngo, Q.-M., et al. (2009) · Nature · doi:10.1038/nature08514 · Cited by 4,673 · see citing works
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302 · see citing works
Self-citationEstablishing, maintaining and modifying DNA methylation patterns in plants and animals
Law, J. A., & Jacobsen, S. E. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2719 · Cited by 3,868 · see citing works
The Polycomb complex PRC2 and its mark in life
Margueron, R., & Reinberg, D. (2011) · Nature · doi:10.1038/nature09784 · Cited by 3,347 · see citing works
CpG islands and the regulation of transcription
Deaton, A. M., & Bird, A. (2011) · Genes & Development · doi:10.1101/gad.2037511 · Cited by 3,187 · see citing works
DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045 · see citing works
Self-citationA decade of exploring the cancer epigenome—biological and translational implications
Baylin, S. B., & Jones, P. A. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3130 · Cited by 2,871 · see citing works
Epigenetic modifications and human disease
Portela, A., & Esteller, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1685 · Cited by 2,843 · see citing works
Linking DNA methylation and histone modification: patterns and paradigms
Cedar, H., & Bergman, Y. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2540 · Cited by 2,267 · see citing works
methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles
Akalin, A., Kormáksson, M., Li, S., Garrett-Bakelman, F. E., Figueroa, M. E., Melnick, A. M., & Mason, C. E. (2012) · Genome biology · doi:10.1186/gb-2012-13-10-r87 · Cited by 2,205 · see citing works
The NIH Roadmap Epigenomics Mapping Consortium
Bernstein, B. E., Stamatoyannopoulos, J. A., Costello, J. F., Ren, B., Milosavljevic, A., Meissner, A., Kellis, M., Marra, M. A., Beaudet, A. L., Ecker, J. R., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt1010-1045 · Cited by 1,892 · see citing works
Self-citationSturm, D., Witt, H., Hovestadt, V., Khuong-Quang, D.-A., Jones, D. T. W., Konermann, C., Pfaff, E., Tönjes, M., Sill, M., Bender, S., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.08.024 · Cited by 1,828 · see citing works
Self-citationConserved role of intragenic DNA methylation in regulating alternative promoters
Maunakea, A. K., Nagarajan, R. P., Bilenky, M., Ballinger, T. J., D’Souza, C., Fouse, S. D., Johnson, B. E., Hong, C., Nielsen, C., Zhao, Y., et al. (2010) · Nature · doi:10.1038/nature09165 · Cited by 1,743 · see citing works
Principles and challenges of genome-wide DNA methylation analysis
Laird, P. W. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2732 · Cited by 1,574 · see citing works
A User's Guide to the Encyclopedia of DNA Elements (ENCODE)
The ENCODE Project Consortium (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001046 · Cited by 1,495 · see citing works
Dissecting direct reprogramming through integrative genomic analysis
Mikkelsen, T. S., Hanna, J. H., Zhang, X., Ku, M., Wernig, M., Schorderet, P., Bernstein, B., Jaenisch, R., Lander, E. S., & Meissner, A. (2008) · Nature · doi:10.1038/nature07056 · Cited by 1,472 · see citing works
Self-citationDirect detection of DNA methylation during single-molecule, real-time sequencing
Flusberg, B. A., Webster, D. R., Lee, J. H., Travers, K. J., Olivares, E. C., Clark, T. A., Korlach, J., & Turner, S. W. (2010) · Nature Methods · doi:10.1038/nmeth.1459 · Cited by 1,460 · see citing works
DNA-binding factors shape the mouse methylome at distal regulatory regions
Stadler, M. B., Murr, R., Burger, L., Ivanek, R., Lienert, F., Schöler, A., Nimwegen, E. V., Wirbelauer, C., Oakeley, E. J., Gaidatzis, D., et al. (2011) · Nature · doi:10.1038/nature10716 · Cited by 1,383 · see citing works
Charting a dynamic DNA methylation landscape of the human genome
Ziller, M. J., Gu, H., Müller, F., Donaghey, J., Tsai, L. T.-Y., Kohlbacher, O., De Jager, P. L., Rosen, E. D., Bennett, D. A., Bernstein, B. E., et al. (2013) · Nature · doi:10.1038/nature12433 · Cited by 1,357 · see citing works
Self-citationHigh-Throughput Sequencing Technologies
Reuter, J., Spacek, D. V., & Snyder, M. P. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.004 · Cited by 1,330 · see citing works
BSMAP: whole genome bisulfite sequence MAPping program
Xi, Y., & Li, W. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-232 · Cited by 1,216 · see citing works
Cancer epigenetics reaches mainstream oncology
Rodríguez‐Paredes, M., & Esteller, M. (2011) · Nature Medicine · doi:10.1038/nm.2305 · Cited by 1,207 · see citing works
Architectural protein subclasses shape 3D organization of genomes during lineage commitment
Phillips-Cremins, J. E., Sauria, M. E. G., Sanyal, A., Gerasimova, T. I., Lajoie, B. R., Bell, J. S. K., Ong, C.-T., Hookway, T. A., Guo, C., Sun, Y., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.053 · Cited by 1,187 · see citing works
Cancer Genetics and Epigenetics: Two Sides of the Same Coin?
You, J. S., & Jones, P. A. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.06.008 · Cited by 1,163 · see citing works
Carone, B. R., Fauquier, L., Habib, N., Shea, J. M., Hart, C. E., Li, R., Bock, C., Li, C., Gu, H., Zamore, P. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.12.008 · Cited by 1,157 · see citing works
Self-citationCharting histone modifications and the functional organization of mammalian genomes
Zhou, V. W., Goren, A., & Bernstein, B. E. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2905 · Cited by 1,147 · see citing works
Self-citationDnmt3a is essential for hematopoietic stem cell differentiation
Challen, G. A., Sun, D., Jeong, M., Luo, M., Jelinek, J., Berg, J. S., Bock, C., Vasanthakumar, A., Gu, H., Xi, Y., et al. (2012) · Nature Genetics · doi:10.1038/ng.1009 · Cited by 1,122 · see citing works
Self-citationDynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation
Ficz, G., Branco, M. R., Seisenberger, S., Santos, F., Krueger, F., Hore, T. A., Marques, C. J., Andrews, S., & Reik, W. (2011) · Nature · doi:10.1038/nature10008 · Cited by 1,123 · see citing works
Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells
Ball, M. P., Li, J. B., Gao, Y., Lee, J., LeProust, E. M., Park, I., Xie, B., Daley, G. Q., & Church, G. M. (2009) · Nature Biotechnology · doi:10.1038/nbt.1533 · Cited by 1,087 · see citing works
Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine
Song, C., Szulwach, K. E., Fu, Y., Dai, Q., Yi, C., Li, X., Li, Y., Chen, C.-H., Zhang, W., Jian, X., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1732 · Cited by 1,089 · see citing works
Dna Hypomethylation In Cancer Cells
Ehrlich, M. (2009) · Epigenomics · doi:10.2217/epi.09.33 · Cited by 1,065 · see citing works
Molecular Maps of the Reorganization of Genome-Nuclear Lamina Interactions during Differentiation
Peric-Hupkes, D., Meuleman, W., Pagie, L., Bruggeman, S. W. M., Solovei, I., Brugman, W., Gräf, S., Flicek, P., Kerkhoven, R. M., van Lohuizen, M., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.03.016 · Cited by 1,050 · see citing works
Initial impact of the sequencing of the human genome
Lander, E. S. (2011) · Nature · doi:10.1038/nature09792 · Cited by 1,044 · see citing works
Self-citationNCBI GEO: archive for high-throughput functional genomic data
Barrett, T., Troup, D. B., Wilhite, S. E., Ledoux, P., Rudnev, D., Evangelista, C., Kim, I. F., Soboleva, A., Tomashevsky, M., Marshall, K. A., et al. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn764 · Cited by 1,043 · see citing works
Dynamic changes in the human methylome during differentiationPreprint
Laurent, L. C., Wong, E., Li, G., Huynh, T., Tsirigos, A., Ong, C. T., Low, H. M., Sung, K. W. K., Rigoutsos, I., Loring, J. F., et al. (2010) · Genome Research · doi:10.1101/gr.101907.109 · Cited by 1,037 · see citing works
Khuong-Quang, D.-A., Buczkowicz, P., Rakopoulos, P., Liu, X.-Y., Fontebasso, A. M., Bouffet, E., Bartels, U., Albrecht, S., Schwartzentruber, J., Letourneau, L., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0998-0 · Cited by 1,028 · see citing works
Bock, C., Kiskinis, E., Verstappen, G., Gu, H., Boulting, G., Smith, Z. D., Ziller, M., Croft, G. F., Amoroso, M. W., Oakley, D. H., et al. (2011) · Cell · doi:10.1016/j.cell.2010.12.032 · Cited by 1,009 · see citing works
Self-citationTET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity
Williams, K., Christensen, J., Pedersen, M. T., Johansen, J. V., Cloos, P. A. C., Rappsilber, J., & Helin, K. (2011) · Nature · doi:10.1038/nature10066 · Cited by 1,021 · see citing works
Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains
Ku, M., Koche, R. P., Rheinbay, E., Mendenhall, E. M., Endoh, M., Mikkelsen, T. S., Aiden, A. P., Nusbaum, C., Xie, X. S., Chi, A. S., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000242 · Cited by 1,011 · see citing works
Self-citationDNA methylation pathways and their crosstalk with histone methylation
Du, J., Johnson, L. M., Jacobsen, S. E., & Patel, D. J. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4043 · Cited by 1,000 · see citing works
Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome
Sandoval, J., Heyn, H., Moran, S., Serra-Musach, J., Pujana, M. A., Bibikova, M., & Esteller, M. (2011) · Epigenetics · doi:10.4161/epi.6.6.16196 · Cited by 990 · see citing works
A unique regulatory phase of DNA methylation in the early mammalian embryo
Smith, Z. D., Chan, M. M., Mikkelsen, T. S., Gu, H., Gnirke, A., Regev, A., & Meissner, A. (2012) · Nature · doi:10.1038/nature10960 · Cited by 964 · see citing works
Self-citationQuantitative Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution
Booth, M. J., Branco, M. R., Ficz, G., Oxley, D., Krueger, F., Reik, W., & Balasubramanian, S. (2012) · Science · doi:10.1126/science.1220671 · Cited by 923 · see citing works
Molecular Signals of Epigenetic States
Bonasio, R., Tu, S., & Reinberg, D. (2010) · Science · doi:10.1126/science.1191078 · Cited by 912 · see citing works
Illingworth, R. S., & Bird, A. P. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.04.012 · Cited by 881 · see citing works
DNA methylation: a historical perspective
Mattei, A. L., Bailly, N., & Meissner, A. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.03.010 · Cited by 876 · see citing works
Self-citationGenome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency
Popp, C., Dean, W., Feng, S., Cokus, S. J., Andrews, S., Pellegrini, M. A., Jacobsen, S. E., & Reik, W. (2010) · Nature · doi:10.1038/nature08829 · Cited by 860 · see citing works
Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers
Okugawa, Y., Grady, W. M., & Goel, A. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.07.011 · Cited by 782 · see citing works
Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain
Gibbs, J. R., van der Brug, M. P., Hernandez, D. G., Traynor, B. J., Nalls, M. A., Lai, S.-L., Arepalli, S., Dillman, A., Rafferty, I. P., Troncoso, J., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000952 · Cited by 769 · see citing works
A double take on bivalent promotersPreprint
Voigt, P., Tee, W., & Reinberg, D. (2013) · Genes & Development · doi:10.1101/gad.219626.113 · Cited by 811 · see citing works
Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells
Pastor, W. A., Pape, U. J., Huang, Y., Henderson, H. R., Lister, R., Ko, M., McLoughlin, E. M., Brudno, Y., Mahapatra, S., Kapranov, P., et al. (2011) · Nature · doi:10.1038/nature10102 · Cited by 804 · see citing works
Defining cell types and states with single-cell genomics
Trapnell, C. (2015) · Genome Research · doi:10.1101/gr.190595.115 · Cited by 813 · see citing works
Distinct epigenomic landscapes of pluripotent and lineage-committed human cells
Hawkins, R. D., Hon, G. C., Lee, L. K., Ngo, Q., Lister, R., Pelizzola, M., Edsall, L. E., Kuan, S., Luu, Y., Klugman, S., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.03.018 · Cited by 806 · see citing works
Koh, K. P., Yabuuchi, A., Rao, S., Huang, Y., Cunniff, K., Nardone, J., Laiho, A., Tahiliani, M., Sommer, C. A., Mostoslavsky, G., et al. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.01.008 · Cited by 776 · see citing works
Epigenetics in Alternative Pre-mRNA Splicing
Luco, R. F., Alló, M., Schor, I. E., Kornblihtt, A. R., & Misteli, T. (2011) · Cell · doi:10.1016/j.cell.2010.11.056 · Cited by 783 · see citing works
Mertens, J., Paquola, A. C. M., Ku, M., Hatch, E., Böhnke, L., Ladjevardi, S., McGrath, S., Campbell, B., Lee, H., Herdy, J. R., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.09.001 · Cited by 765 · see citing works
Gu, H., Smith, Z. D., Bock, C., Boyle, P., Gnirke, A., & Meissner, A. (2011) · Nature Protocols · doi:10.1038/nprot.2010.190 · Cited by 750 · see citing works
Self-citationHuman aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domainsPreprint
Rakyan, V. K., Down, T. A., Maslau, S., Andrew, T., Yang, T.-P., Beyan, H., Whittaker, P., McCann, O. T., Finer, S., Valdes, A. M., et al. (2010) · Genome Research · doi:10.1101/gr.103101.109 · Cited by 750 · see citing works
Chromatin structure and the inheritance of epigenetic information
Margueron, R., & Reinberg, D. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2752 · Cited by 733 · see citing works
Epigenomic Analysis of Multilineage Differentiation of Human Embryonic Stem Cells
Xie, W., Schultz, M. D., Lister, R., Hou, Z., Rajagopal, N., Ray, P. R., Whitaker, J. W., Tian, S., Hawkins, R. D., Leung, D., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.022 · Cited by 721 · see citing works
DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryosPreprint
Messerschmidt, D. M., Knowles, B. B., & Solter, D. (2014) · Genes & Development · doi:10.1101/gad.234294.113 · Cited by 734 · see citing works
Sun, D., Luo, M., Jeong, M., Rodriguez, B., Xia, Z., Hannah, R., Wang, H., Le, T., Faull, K. F., Chen, R., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.03.002 · Cited by 686 · see citing works
Self-citationThe Behaviour of 5-Hydroxymethylcytosine in Bisulfite Sequencing
Huang, Y., Pastor, W., Shen, Y.-H., Tahiliani, M., Liu, D. R., & Rao, A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008888 · Cited by 755 · see citing works
Biases in Illumina transcriptome sequencing caused by random hexamer priming
Hansen, K. D., Brenner, S. E., & Dudoit, S. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq224 · Cited by 713 · see citing works
Harris, R. A., Wang, T., Coarfa, C., Nagarajan, R. P., Hong, C., Downey, S. L., Johnson, B., Fouse, S. D., Delaney, A. D., Zhao, Y., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1682 · Cited by 713 · see citing works
Self-citationTranscription factors as readers and effectors of DNA methylation
Zhu, H., Wang, G., & Qian, J. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.83 · Cited by 649 · see citing works
Dynamic DNA methylation across diverse human cell lines and tissuesPreprint
Varley, K. E., Gertz, J., Bowling, K. M., Parker, S. L., Reddy, T. E., Pauli, F., Cross, M. K., Williams, B. A., Stamatoyannopoulos, J. A., Crawford, G. E., et al. (2013) · Genome Research · doi:10.1101/gr.147942.112 · Cited by 693 · see citing works
Dynamic CpG island methylation landscape in oocytes and preimplantation embryos
Smallwood, S. A., Tomizawa, S.-I., Krueger, F., Ruf, N., Carli, N., Segonds-Pichon, A., Sato, S., Hata, K., Andrews, S., & Kelsey, G. (2011) · Nature Genetics · doi:10.1038/ng.864 · Cited by 701 · see citing works
Pluripotency and Cellular Reprogramming: Facts, Hypotheses, Unresolved Issues
Hanna, J. H., Saha, K., & Jaenisch, R. (2010) · Cell · doi:10.1016/j.cell.2010.10.008 · Cited by 695 · see citing works
Self-citationStructure and Function of Mammalian DNA Methyltransferases
Jurkowska, R. Z., Jurkowski, T. P., & Jeltsch, A. (2010) · ChemBioChem · doi:10.1002/cbic.201000195 · Cited by 694 · see citing works
Core, L. J., Martins, A. L., Danko, C. G., Waters, C. T., Siepel, A., & Lis, J. T. (2014) · Nature Genetics · doi:10.1038/ng.3142 · Cited by 693 · see citing works
Epigenetics in health and disease
Zhang, L., Lu, Q., & Chang, C. (2020) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-15-3449-2_1 · Cited by 689 · see citing works
Epigenetic control of T-helper-cell differentiation
Wilson, C. B., Rowell, E. A., & Sekimata, M. (2009) · Nature reviews. Immunology · doi:10.1038/nri2487 · Cited by 678 · see citing works
Germline Competent Embryonic Stem Cells Derived from Rat Blastocysts
Li, P., Tong, C., Mehrian‐Shai, R., Li, J., Wu, N. L., Yan, Y., Maxson, R. E., Schulze, E. N., Song, H., Hsieh, C., et al. (2008) · Cell · doi:10.1016/j.cell.2008.12.006 · Cited by 679 · see citing works
Induced Pluripotent Stem Cell Generation Using a Single Lentiviral Stem Cell Cassette
Sommer, C. A., Stadtfeld, M., Murphy, G. J., Hochedlinger, K., Kotton, D. N., & Mostoslavsky, G. (2009) · Stem Cells · doi:10.1634/stemcells.2008-1075 · Cited by 676 · see citing works
Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidationPreprint
Wu, H., & Zhang, Y. (2011) · Genes & Development · doi:10.17615/800j-yk16 · Cited by 665 · see citing works
Neuronal activity modifies the DNA methylation landscape in the adult brain
Guo, J. U., Ma, D. K., Mo, H., Ball, M. P., Jang, M.-H., Bonaguidi, M. A., Balazer, J. A., Eaves, H. L., Xie, B., Ford, E., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2900 · Cited by 669 · see citing works
Genome-Wide Demethylation of Arabidopsis Endosperm
Hsieh, T., Ibarra, C. A., Silva, P., Zemach, A., Williams, L. E., Fischer, R. L., & Zilberman, D. (2009) · Science · doi:10.1126/science.1172417 · Cited by 652 · see citing works
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells
Wu, H., D’Alessio, A. C., Ito, S., Xia, K., Wang, Z., Cui, K., Zhao, K., Eve Sun, Y., & Zhang, Y. (2011) · Nature · doi:10.1038/nature09934 · Cited by 646 · see citing works
DNA Methylation of the First Exon Is Tightly Linked to Transcriptional Silencing
Brenet, F. A., Moh, M., Funk, P., Feierstein, E., Viale, A. J., Socci, N. D., & Scandura, J. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014524 · Cited by 627 · see citing works
CpG islands influence chromatin structure via the CpG-binding protein Cfp1
Thomson, J. P., Skene, P. J., Selfridge, J., Clouaire, T., Guy, J., Webb, S., Kerr, A. R. W., Deaton, A., Andrews, R., James, K. D., et al. (2010) · Nature · doi:10.1038/nature08924 · Cited by 625 · see citing works
Xu, Y., Wu, F., Tan, L., Kong, L., Xiong, L., Deng, J., Barbera, A. J., Zheng, L., Zhang, H., Huang, S., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.04.005 · Cited by 634 · see citing works
DNA methylation signatures link prenatal famine exposure to growth and metabolism
Tobi, E. W., Goeman, J. J., Monajemi, R., Gu, H., Putter, H., Zhang, Y., Slieker, R. C., Stok, A. P., Thijssen, P. E., Müller, F., et al. (2014) · Nature Communications · doi:10.1038/ncomms6592 · Cited by 630 · see citing works
Self-citationChild Health, Developmental Plasticity, and Epigenetic Programming
Hochberg, Z., Feil, R., Constância, M., Fraga, M. F., Junien, C., Carel, J., Boileau, P., Bouc, Y. L., Deal, C., Lillycrop, K. A., et al. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0039 · Cited by 631 · see citing works
Chromatin modifiers and remodellers: regulators of cellular differentiation
Chen, T., & Dent, S. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3607 · Cited by 629 · see citing works
Epigenetic mechanisms that underpin metabolic and cardiovascular diseases
Gluckman, P. D., Hanson, M. A., Buklijas, T., Low, F. M., & Beedle, A. S. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.102 · Cited by 627 · see citing works
CTCF-mediated functional chromatin interactome in pluripotent cells
Handoko, L., Han, X., Li, G., Ngan, C. Y., Chew, E. G. Y., Schnapp, M., Lee, C. W. H., Ye, C., Ping, J. L. H., Mulawadi, F. H., et al. (2011) · Nature Genetics · doi:10.1038/ng.857 · Cited by 614 · see citing works
Lee, W., Teckie, S., Wiesner, T., Ran, L., Granada, C. N. P., Lin, M., Zhu, S., Cao, Z., Liang, Y., Sboner, A., et al. (2014) · Nature Genetics · doi:10.1038/ng.3095 · Cited by 618 · see citing works
Cui, K., Zang, C., Roh, T., Schones, D. E., Childs, R. W., Peng, W., & Zhao, K. (2009) · Cell stem cell · doi:10.1016/j.stem.2008.11.011 · Cited by 620 · see citing works
Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes
Wu, H., Coskun, V., Tao, J., Xie, W., Ge, W., Yoshikawa, K., Li, E., Zhang, Y., & Sun, Y. E. (2010) · Science · doi:10.1126/science.1190485 · Cited by 604 · see citing works
Targets and dynamics of promoter DNA methylation during early mouse development
Borgel, J., Guibert, S., Li, Y., Chiba, H., Schübeler, D., Sasaki, H., Forné, T., & Weber, M. (2010) · Nature Genetics · doi:10.1038/ng.708 · Cited by 602 · see citing works
Quantitative comparison of genome-wide DNA methylation mapping technologies
Bock, C., Tomazou, E. M., Brinkman, A. B., Müller, F., Simmer, F., Gu, H., Jäger, N., Gnirke, A., Stunnenberg, H. G., & Meissner, A. (2010) · Nature Biotechnology · doi:10.1038/nbt.1681 · Cited by 587 · see citing works
Self-citationNext-generation genomics: an integrative approach
Hawkins, R. D., Hon, G. C., & Ren, B. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2795 · Cited by 591 · see citing works
DNA methylation dynamics in health and disease
Bergman, Y., & Cedar, H. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2518 · Cited by 592 · see citing works
Genome-Wide Dna Methylation Profiling Using Infinium ® Assay
Bibikova, M. V., Le, J. M., Barnes, B., Saedinia-Melnyk, S., Zhou, L., Shen, R., & Gunderson, K. L. (2009) · Epigenomics · doi:10.2217/epi.09.14 · Cited by 592 · see citing works
- Authors
- Meissner, A., Mikkelsen, T. S., Gu, H., Wernig, M., Hanna, J., Sivachenko, A., Zhang, X., Bernstein, B. E., Nusbaum, C., Jaffe, D. B., Gnirke, A., Jaenisch, R., & Lander, E. S.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Broad Institute (US)
- Corresponding author
- Jaenisch, Rudolf
- Lander, Eric S.
- ORCID
- Venue
- Nature
- Published
- 2008-07-06
- Volume
- 454
- Issue
- 7205
- Pages
- 766-770
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2896277
- OpenAlex
- W2161224111
- Cited by
- 2,536
- References
- 30
- Citations by year
- 2026: 40 · 2025: 53 · 2024: 74 · 2023: 81 · 2022: 73 · 2021: 124 · 2020: 91 · 2019: 110 · 2018: 102 · 2017: 141 · 2016: 138 · 2015: 192 · 2014: 194 · 2013: 218 · 2012: 230
- FWCI
- 91.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Broad Institute
- National Human Genome Research Institute (R01HG004401, U54HG003067)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- DNA methylation, embryonic stem cells, cell differentiation, CpG islands, histone methylation, epigenetic profiling, neural cells, hypermethylation, transposable elements, conserved non-coding elements, mice, cancer epigenetics, regenerative medicine
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Fibroblasts, Histones, Male, Neurons, Genome, Conserved Sequence, CpG Islands, DNA Methylation, Genomics, Pluripotent Stem Cells, Mice, Embryonic Stem Cells
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