Human body epigenome maps reveal noncanonical DNA methylation variation

Schultz, Matthew D.; He, Yiping; Whitaker, John W.; Hariharan, Manoj; Mukamel, Eran A.; Leung, Danny; Rajagopal, Nisha; Nery, Joseph R.; Urich, Mark A.; Chen, Huaming; Lin, Shin; Lin, Yiing; Jung, Inkyung; Schmitt, Anthony; Selvaraj, Siddarth; Ren, Bing; Sejnowski, Terrence J.; Wang, Wei; Ecker, Joseph R.

doi:10.1038/nature14465

Cited by 612 publications

(642 citation statements)

References 30 publications

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“…Finally, we also analyzed the data from 980 probes in non‐CpG sequence context. In agreement with recently published data (Schultz et al ., 2015), we detected low, but significant levels of non‐CpG methylation in the human epidermis (Fig. S4).…”

Section: Resultsmentioning

confidence: 83%

Reduced DNA methylation patterning and transcriptional connectivity define human skin aging

et al. 2016

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SummaryEpigenetic changes represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Age‐related changes in DNA methylation at the genome scale have been termed ‘epigenetic drift’, but the defining features of this phenomenon remain to be established. Human epidermis represents an excellent model for understanding age‐related epigenetic changes because of its substantial cell‐type homogeneity and its well‐known age‐related phenotype. We have now generated and analyzed the currently largest set of human epidermis methylomes (N = 108) using array‐based profiling of 450 000 methylation marks in various age groups. Data analysis confirmed that age‐related methylation differences are locally restricted and characterized by relatively small effect sizes. Nevertheless, methylation data could be used to predict the chronological age of sample donors with high accuracy. We also identified discontinuous methylation changes as a novel feature of the aging methylome. Finally, our analysis uncovered an age‐related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks. Our findings thus define the loss of epigenetic regulatory fidelity as a key feature of the aging epigenome.

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Section: Resultsmentioning

confidence: 83%

Reduced DNA methylation patterning and transcriptional connectivity define human skin aging

et al. 2016

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“…Cell-line and tissue-specific DNA modifications are central features of multicellular development, and there are substantial differences in DNA methylation between different cell and tissue types in both humans and plants 19,20 . Understanding how these elements impact cellular activity is important for linking epigenetic changes with phenotypes.…”

Section: Analysis Of Dap-seq Datamentioning

confidence: 99%

Mapping genome-wide transcription-factor binding sites using DAP-seq

Bartlett¹,

O’Malley²,

Huang³

et al. 2017

Nat Protoc

400

285

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In order to enable low-cost, high-throughput generation of cistrome and epicistrome maps for any organism, we developed DNA affinity purification sequencing (DAP-seq), a transcription factor (TF) binding site discovery assay that couples affinity-purified TFs with next-generation sequencing of a genomic DNA library. The method is fast, inexpensive, and more easily scaled than ChIP-seq. DNA libraries are constructed using native genomic DNA from any source of interest, preserving cell-and tissue-specific chemical modifications that are known to impact TF binding (such as DNA methylation) and providing increased specificity compared to in silico motif prediction methods such as protein binding microarrays (PBM) and systematic evolution of ligands by exponential enrichment (SELEX). The resulting DNA library is incubated with an affinity-tagged in vitro expressed TF, and TF-DNA complexes are purified using magnetic separation of the affinity tag. Bound genomic DNA is eluted from the TF and sequenced using next-generation sequencing. Sequence reads are mapped to a reference genome, identifying genome-wide binding locations for each TF assayed, from which sequence motifs can then be

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“…Surveys of DNA methylation in human tissues have established a complex landscape, including both tissuespecific and invariant methylation patterns. 24 Current models suggest that DNA methylation helps counteract chromatin disruption, as found in nucleosome displacement during RNAP elongation, for example, while CG-poor regulatory regions generally acquire a low methylation state when occupied by transcription factors (reviewed in 23 ).…”

Section: Dna Methylationmentioning

confidence: 99%

Epigenetic modification in chromatin machinery and its deregulation in pediatric brain tumors: Insight into epigenetic therapies

Maury

Hashizume

2017

Epigenetics

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Malignancies are characterized by the reprogramming of epigenetic patterns. This reprogramming includes gains or losses in DNA methylation and disruption of normal patterns of covalent histone modifications, which are associated with changes in chromatin remodeling processes. This review will focus on the mechanisms underlying this reprogramming and, specifically, on the role of histone modification in chromatin machinery and the modifications in epigenetic processes occurring in brain cancer, with a specific focus on epigenetic therapies for pediatric brain tumors.

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Human body epigenome maps reveal noncanonical DNA methylation variation

Cited by 612 publications

References 30 publications

Reduced DNA methylation patterning and transcriptional connectivity define human skin aging

Reduced DNA methylation patterning and transcriptional connectivity define human skin aging

Mapping genome-wide transcription-factor binding sites using DAP-seq

Epigenetic modification in chromatin machinery and its deregulation in pediatric brain tumors: Insight into epigenetic therapies

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