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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MiR-27a functions as a tumor suppressor in acute leukemia by regulating 14-3-3θ.
Kara A. Scheibner,Brianne Teaboldt,Mary Claire Hauer,Xiaochun Chen,Srujana Cherukuri,Yin Guo,Shannon M. Kelley,Zhenqiu Liu,Maria R. Baer,Shelly Heimfeld,Curt I. Civin +10 more
TL;DR: The data indicate that miR-27a contributes a tumor suppressor-like activity in acute leukemia cells via regulation of apoptosis, and thatmiR- 27a and 14-3-3θ may be potential therapeutic targets.
Journal ArticleDOI
Maternal vitamin C regulates reprogramming of DNA methylation and germline development
Stephanie P. DiTroia,Michelle Percharde,Marie Justine Guerquin,Estelle Wall,Evelyne Collignon,Kevin T. Ebata,Kathryn Mesh,Swetha Mahesula,Michalis Agathocleous,Diana J. Laird,Gabriel Livera,Miguel Ramalho-Santos,Miguel Ramalho-Santos +12 more
TL;DR: It is shown that maternal vitamin C is required for proper DNA demethylation and the development of female fetal germ cells in a mouse model, and deficiency in vitamin C during gestation partially recapitulates loss of TET1, and provide a potential intergenerational mechanism for adjusting fecundity to environmental conditions.
Journal ArticleDOI
Tissue-specific variation in DNA methylation levels along human chromosome 1
Cecilia De Bustos,Cecilia De Bustos,Edward Ramos,Edward Ramos,Edward Ramos,Janet M. Young,Robert K. Tran,Robert K. Tran,Uwe Menzel,Cordelia Langford,Evan E. Eichler,Evan E. Eichler,Li Hsu,Steve Henikoff,Steve Henikoff,Jan P. Dumanski,Barbara J. Trask,Barbara J. Trask +17 more
TL;DR: The varied patterns of methylation differences detected between tissues by the methylation profiling method reinforce the potential functional significance of regional differences in methylation levels outside of CpG islands.
Journal ArticleDOI
RUNX1 regulates site specificity of DNA demethylation by recruitment of DNA demethylation machineries in hematopoietic cells.
Takahiro Suzuki,Yuri Shimizu,Erina Furuhata,Shiori Maeda,Mami Kishima,Hajime Nishimura,Saaya Enomoto,Yoshihide Hayashizaki,Harukazu Suzuki +8 more
TL;DR: Zhang et al. as mentioned in this paper demonstrate that RUNX1 contributes DNA demethylation in a binding site-directed manner in human hematopoietic cells. But the role of the epigenetic role of runx1 remains unclear.
Journal ArticleDOI
Identification of DNA methylation changes associated with human gastric cancer
Jung Hoon Park,Jinah Park,Jung Kyoon Choi,Jung Kyoon Choi,Jaemyun Lyu,Min Gyun Bae,Young Gun Lee,Jae Bum Bae,Dong Yoon Park,Han-Kwang Yang,Tae-You Kim,Young Joon Kim +11 more
TL;DR: Gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA, indicating that methylation of specific genes is gradually increased in cancerous tissue.
References
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Journal ArticleDOI
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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Journal ArticleDOI
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
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TL;DR: Insight is given into the connections between chromatin modifications and transcriptional regulatory activity and a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2) is uncovered, providing a new tool for the functional annotation of the human genome.
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