The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Dynamic changes in the human methylome during differentiation
Open accessAbstract
DNA methylation is a critical epigenetic regulator in mammalian development. Here, we present a whole-genome comparative view of DNA methylation using bisulfite sequencing of three cultured cell types representing progressive stages of differentiation: human embryonic stem cells (hESCs), a fibroblastic differentiated derivative of the hESCs, and neonatal fibroblasts. As a reference, we compared our maps with a methylome map of a fully differentiated adult cell type, mature peripheral blood mononuclear cells (monocytes). We observed many notable common and cell-type-specific features among all cell types. Promoter hypomethylation (both CG and CA) and higher levels of gene body methylation were positively correlated with transcription in all cell types. Exons were more highly methylated than introns, and sharp transitions of methylation occurred at exon–intron boundaries, suggesting a role for differential methylation in transcript splicing. Developmental stage was reflected in both the level of global methylation and extent of non-CpG methylation, with hESC highest, fibroblasts intermediate, and monocytes lowest. Differentiation-associated differential methylation profiles were observed for developmentally regulated genes, including the HOX clusters, other homeobox transcription factors, and pluripotence-associated genes such as POU5F1 , TCF3 , and KLF4 . Our results highlight the value of high-resolution methylation maps, in conjunction with other systems-level analyses, for investigation of previously undetectable developmental regulatory mechanisms.
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Cites
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
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Epigenetic Reprogramming in Mammalian Development
Reik, W., Dean, W., & Walter, J. (2001) · Science · doi:10.1126/science.1063443 · Cited by 3,078
Genome-scale DNA methylation maps of pluripotent and differentiated cells
Meissner, A., Mikkelsen, T. S., Gu, H., Wernig, M., Hanna, J., Sivachenko, A., Zhang, X., Bernstein, B. E., Nusbaum, C., Jaffe, D. B., et al. (2008) · Nature · doi:10.1038/nature07107 · Cited by 2,536
Transcription of IAP endogenous retroviruses is constrained by cytosine methylation
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The diploid genome sequence of an Asian individual
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Self-citationChromatin organization marks exon-intron structure
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The human SWI/SNF subunit Brm is a regulator of alternative splicing
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Regulatory networks define phenotypic classes of human stem cell lines
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Cited by
Functions of DNA methylation: islands, start sites, gene bodies and beyond
Jones, P. A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3230 · Cited by 6,061
DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045
High density DNA methylation array with single CpG site resolution
Bibikova, M., Barnes, B., Tsan, C., Ho, V., Klotzle, B., Le, J. M., Delano, D., Zhang, L., Schroth, G. P., Gunderson, K. L., et al. (2011) · Genomics · doi:10.1016/j.ygeno.2011.07.007 · Cited by 1,727
“Other categories represented were non-CpG sites [9,31], DNase hypersensitive sites [32,33] and differentially methylated regions [18,34].”
BackgroundCharting 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
The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells
Seisenberger, S., Andrews, S., Krueger, F., Arand, J., Walter, J., Santos, F., Popp, C., Thienpont, B., Dean, W., & Reik, W. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.11.001 · Cited by 973
Metadata
- Authors
- Laurent, L., Wong, E., Li, G., Huynh, T., Tsirigos, A., Ong, C. T., Low, H. M., Kin Sung, K. W., Rigoutsos, I., Loring, J., & Wei, C.-L.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-02-04
- Volume
- 20
- Issue
- 3
- Pages
- 320-331
- ISSN
- 1088-9051 (ISSN-L)
- OpenAlex
- W1986849101
- Cited by
- 1,041
- References
- 9
- Type
- posted content
- Language
- en
- Open access
- hybrid
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- Laurent, L., Wong, E., Li, G., Huynh, T., Tsirigos, A., Ong, C. T., Low, H. M., Kin Sung, K. W., Rigoutsos, I., Loring, J., & Wei, C.-L. (2010). Dynamic changes in the human methylome during differentiation. Genome Research. https://doi.org/10.1101/gr.101907.109
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