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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Journal ArticleDOI
DNA Methylation Plasticity of Human Adipose-Derived Stem Cells in Lineage Commitment
María Berdasco,Consolación Melguizo,Jose Prados,Antonio Gomez,Miguel Alaminos,Miguel Angel Pujana,Miguel Lopez,Fernando Setien,Raúl Ortiz,Inma Zafra,Antonia Aránega,Manel Esteller,Manel Esteller +12 more
TL;DR: It is shown that human adipose-derived stem cells generate myogenic and osteogenic lineages that share much of the DNA methylation landscape characteristic of primary myocytes and osteocytes, and that these cells could be used for clinical purposes as a biomarker of efficient and safely differentiated cells.
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Epigenetic regulation of stem cells differentiating along the neural lineage.
TL;DR: Collectively, a complex epigenetic network formed by H3K4me3, histone acetylation/deacetylation, H 3K27me3 and DNA methylation/demethylation act together to regulate stem cell self-renewal and differentiation.
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The meta-epigenomic structure of purified human stem cell populations is defined at cis-regulatory sequences.
N. Ari Wijetunga,Fabien Delahaye,Yong Mei Zhao,Aaron Golden,Jessica C. Mar,Francine H. Einstein,John M. Greally +6 more
TL;DR: Findings of increased variability at loci with intermediate DNA methylation values, at candidate “poised” enhancers, and at genes involved in HSPC lineage commitment suggest that CD34+ cell subtype heterogeneity between individuals is a major mechanism for the variability observed.
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Liquid biopsies: DNA methylation analyses in circulating cell-free DNA.
TL;DR: This review summarizes the various investigational applications of cfDNA methylation and its oxidized derivatives as biomarkers for cancer diagnosis, prenatal diagnosis and organ transplantation monitoring.
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PPARG Epigenetic Deregulation and Its Role in Colorectal Tumorigenesis.
TL;DR: A comprehensive look at the current understanding of the relationship between PPARγ and cancer development is taken and the role that epigenetic mechanisms play is addressed, disclosing novel crosstalks betweenPPARG signaling and the epigenetic machinery and suggesting how this dysregulation may contribute to colon cancer development.
References
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A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
Bradley E. Bernstein,Tarjei S. Mikkelsen,Tarjei S. Mikkelsen,Xiaohui Xie,Michael Kamal,Dana J. Huebert,James Cuff,Ben Fry,Alexander Meissner,Marius Wernig,Kathrin Plath,Rudolf Jaenisch,Alexandre Wagschal,Robert Feil,Stuart L. Schreiber,Stuart L. Schreiber,Eric S. Lander,Eric S. Lander +17 more
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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
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