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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Base-Resolution Analyses of Sequence and Parent-of-Origin Dependent DNA Methylation in the Mouse Genome
Wei Xie,Cathy L. Barr,Audrey Kim,Feng Yue,Ah Young Lee,James H. Eubanks,Emma Dempster,Emma Dempster,Bing Ren,Bing Ren +9 more
TL;DR: A base-resolution, allele-specific DNA methylation map in the mouse genome is generated, finding parent-of-origin dependent (imprinted) ASM at 1,952 CG dinucleotides and a surprising presence of non-CG methylation in the adult mouse brain, with some showing evidence of imprinting.
Journal ArticleDOI
Epigenomic Profiling of Young and Aged HSCs Reveals Concerted Changes during Aging that Reinforce Self-Renewal
Deqiang Sun,Min Luo,Mira Jeong,Benjamin Rodriguez,Zheng Xia,Rebecca Hannah,Hui Wang,Thuc Le,Kym F. Faull,Rui Chen,Hongcang Gu,Christoph Bock,Christoph Bock,Alexander Meissner,Berthold Göttgens,Gretchen J. Darlington,Wei Li,Margaret A. Goodell +17 more
TL;DR: A comprehensive integrated genomic analysis of young and aged HSCs showed increased DNA methylation at transcription factor binding sites associated with differentiation-promoting genes combined with a reduction at genes associated with HSC maintenance, paralleling phenotypic HSC aging behavior.
Journal ArticleDOI
DNA methylation dynamics in health and disease
Yehudit Bergman,Howard Cedar +1 more
TL;DR: Dynamics of DNA methylation during normal development in vivo are discussed, starting from fertilization through embryogenesis and postnatal growth, as well as abnormal methylation changes that occur in cancer.
Journal ArticleDOI
Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription
Michael T. Lam,Han Cho,Hanna P. Lesch,David Gosselin,Sven Heinz,Yumiko Tanaka-Oishi,Christopher Benner,Minna U. Kaikkonen,Aneeza Kim,Mika Kosaka,Cindy Y. Lee,Andrew T. Watt,Tamar R. Grossman,Michael G. Rosenfeld,Michael G. Rosenfeld,Ronald M. Evans,Ronald M. Evans,Christopher K. Glass +17 more
TL;DR: Evidence is presented that in mouse macrophages Rev-Erbs regulate target gene expression by inhibiting the functions of distal enhancers that are selected by macrophage-lineage-determining factors, thereby establishing a macrophice-specific program of repression.
Journal ArticleDOI
DNA methylation dynamics of the human preimplantation embryo
Zachary D. Smith,Michelle Chan,Kathryn C. Humm,Rahul Karnik,Shila Mekhoubad,Aviv Regev,Kevin Eggan,Alexander Meissner +7 more
TL;DR: In this paper, the authors present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of residual maintenance are primarily restricted to gene bodies.
References
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