Genome-scale DNA methylation maps of pluripotent and differentiated cells
Alexander Meissner,Tarjei S. Mikkelsen,Tarjei S. Mikkelsen,Hongcang Gu,Marius Wernig,Jacob H. Hanna,Andrey Sivachenko,Xiaolan Zhang,Bradley E. Bernstein,Bradley E. Bernstein,Chad Nusbaum,David B. Jaffe,Andreas Gnirke,Rudolf Jaenisch,Eric S. Lander +14 more
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TLDR
Low-throughput reduced representation bisulphite sequencing is established as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine.Abstract:
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.read more
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Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter
Hui Chen,Hinke G. Kazemier,Marloes L. de Groote,Marcel H. J. Ruiters,Guoliang Xu,Marianne G. Rots +5 more
TL;DR: This work suggests that it provided a mechanism to induce targeted DNA demethylation, which facilitates re-activation of expression of the target genes, and this Epigenetic Editing approach is a powerful tool to investigate functions of epigenetic writers and erasers and to elucidate consequences of epigenetics marks.
Journal ArticleDOI
DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression
Shintaro Yagi,Keiji Hirabayashi,Shinya Sato,Wei Li,Yoko Takahashi,Tsutomu Hirakawa,Guoying Wu,Naoko Hattori,Naka Hattori,Jun Ohgane,Satoshi Tanaka,X. Shirley Liu,Kunio Shiota +12 more
TL;DR: D-REAM, a genome-wide DNA methylation analysis method for tissue-dependent and differentially methylated region (T-DMR) profiling with restriction tag-mediated amplification in mouse tissues and cells, finds that over 3000 T-D MRs are hypomethylated in liver compared to cerebrum, indicating that multilayered regulation of tissue-specific gene function could be elucidated by DNA methylations tissue profiling.
Journal ArticleDOI
Buccals are likely to be a more informative surrogate tissue than blood for epigenome-wide association studies.
Robert Lowe,Carolina Gemma,Huriya Beyan,Mohammed I. Hawa,Alexandra Bazeos,R. David Leslie,Alexandre Montpetit,Vardhman K. Rakyan,Sreeram V. Ramagopalan +8 more
TL;DR: It is proposed that for non-blood based diseases/phenotypes, buccal will be a more informative tissue for genome-wide association studies (GWASs), and Buccal hypo-tDMRs show a statistically significant enrichment near SNPs associated to disease identified through GWASs.
Journal ArticleDOI
Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer
Lingeng Lu,Guangjian Zhu,Chong Zhang,Qian Deng,Qian Deng,Dionyssios Katsaros,Susan T. Mayne,Harvey A. Risch,Lina Mu,Emilie Marion Canuto,Gianluca Gregori,Chiara Benedetto,Herbert Yu,Herbert Yu +13 more
TL;DR: The findings suggest that the intergenic DNA methylation may have important biologic relevance in regulating HotaIR expression, and that HOTAIR expression may not be an independent prognostic marker in breast cancer, but needs further validation in independent studies.
Journal ArticleDOI
Transcriptionally repressed genes become aberrantly methylated and distinguish tumors of different lineages in breast cancer
Duncan Sproul,Colm E. Nestor,Jayne Culley,Jacqueline Dickson,J Michael Dixon,J Michael Dixon,David J. Harrison,Richard R. Meehan,Andrew H. Sims,Bernard H Ramsahoye +9 more
TL;DR: The findings implicate aberrant DNA methylation as a marker of cell lineage rather than tumor progression and suggest that, in most cases, it does not cause the repression with which it is associated.
References
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