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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PBX1 genomic pioneer function drives ERα signaling underlying progression in breast cancer.
TL;DR: Results reveal that PBX1 is a novel pioneer factor defining aggressive ERα-positive breast tumors, as it guides ERα genomic activity to unique genomic regions promoting a transcriptional program favorable to breast cancer progression.
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Lysine-Specific Demethylase 1 Regulates the Embryonic Transcriptome and CoREST Stability
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TL;DR: Lysine-specific demethylase 1 regulates the expression and appropriate timing of key developmental regulators, as part of the LSD1/CoREST/HDAC complex, during early embryonic development.
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Bisulfite sequencing of chromatin immunoprecipitated DNA (BisChIP-seq) directly informs methylation status of histone-modified DNA
Aaron L. Statham,Mark D. Robinson,Jenny Z. Song,Marcel W. Coolen,Clare Stirzaker,Susan J. Clark +5 more
TL;DR: A novel technique based on high-throughput sequencing of bisulfite-treated chromatin immunoprecipitated DNA (BisChIP-seq), which can directly interrogate genetic and epigenetic processes that occur in normal and diseased cells, showed that both methylated and unmethylated alleles can simultaneously be associated with H3K27me3 histones.
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Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer
Jung H. Kim,Saravana M. Dhanasekaran,John R. Prensner,Xuhong Cao,Dan R. Robinson,Shanker Kalyana-Sundaram,Shanker Kalyana-Sundaram,Christina Huang,Sunita Shankar,Xiaojun Jing,Matthew K. Iyer,Ming Hu,Ming Hu,Lee Sam,Catherine S. Grasso,Christopher G. Maher,Nallasivam Palanisamy,Rohit Mehra,Hal D. Kominsky,Javed Siddiqui,Jindan Yu,Zhaohui S. Qin,Arul M. Chinnaiyan +22 more
TL;DR: This comprehensive methylome map will further the understanding of epigenetic regulation in prostate cancer progression and observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion-positive and -negative cancers.
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Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia
Stefanie Göllner,Thomas Oellerich,Thomas Oellerich,Shuchi Agrawal-Singh,Tino Schenk,Hans-Ulrich Klein,Christian Rohde,Caroline Pabst,Tim Sauer,Mads Lerdrup,Sigal Tavor,Friedrich Stölzel,Sylvia Herold,Gerhard Ehninger,Gabriele Köhler,Kuan-Ting Pan,Henning Urlaub,Henning Urlaub,Hubert Serve,Hubert Serve,Martin Dugas,Karsten Spiekermann,Karsten Spiekermann,Binje Vick,Irmela Jeremias,Wolfgang E. Berdel,Klaus Hansen,Arthur Zelent,Claudia Wickenhauser,Lutz P. Müller,Christian Thiede,Carsten Müller-Tidow +31 more
TL;DR: Restoration of EZH2 protein is suggested as a viable approach to overcome treatment resistance in this AML patient population.
References
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