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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Book ChapterDOI
Dynamics of histone lysine methylation: structures of methyl writers and erasers.
Anup K. Upadhyay,Xiaodong Cheng +1 more
TL;DR: Current knowledge on structural and functional properties of various histone lysine methyltransfereases and demethylases are summarized, with emphasis on their importance as druggable targets.
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Elvira Carrió,Anna Díez-Villanueva,Sergi Lois,Izaskun Mallona,Ildefonso Cases,Marta Forn,Miguel A. Peinado,Mònica Suelves +7 more
TL;DR: The unique DNA methylation signature of skeletal muscle stem cells is characterized and the importance ofDNA methylation‐mediated regulation of cell identity Myf5 super‐enhancer during cellular differentiation is highlighted.
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Identification and analysis of murine pancreatic islet enhancers
Bryan R. Tennant,A. G. Robertson,Marabeth M. Kramer,Leping Li,Xuekui Zhang,Mike Beach,Nina Thiessen,R. Chiu,Karen Mungall,Cheryl J. Whiting,Paul V. Sabatini,A. Kim,Raphael Gottardo,Marco A. Marra,Francis C. Lynn,Steven J.M. Jones,Steven J.M. Jones,Pamela A. Hoodless,Brad G. Hoffman +18 more
TL;DR: The results indicate that genes with islet-specific expression and function tend to have enhancers devoid of histone methylation marks or, less often, that are bivalent or repressed, in embryonic stem cells and liver.
Journal ArticleDOI
Epigenome-wide change and variation in DNA methylation in childhood: trajectories from birth to late adolescence.
Rosa H. Mulder,Rosa H. Mulder,Alexander Neumann,Alexander Neumann,Charlotte A.M. Cecil,Charlotte A.M. Cecil,Esther Walton,Esther Walton,Lotte C Houtepen,Andrew J Simpkin,Andrew J Simpkin,Jolien Rijlaarsdam,Bastiaan T. Heijmans,Tom R. Gaunt,Janine F. Felix,Vincent W. V. Jaddoe,Marian J. Bakermans-Kranenburg,Henning Tiemeier,Henning Tiemeier,Caroline L Relton,Marinus H. van IJzendoorn,Marinus H. van IJzendoorn,Matthew Suderman +22 more
TL;DR: A developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease is supported.
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Epigenetic mechanisms involved in developmental nutritional programming.
TL;DR: This review focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics, position and functions of epigenetic marks.
References
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