Whole genome DNA methylation analysis based on high throughput sequencing technology

Li, Ning; Ye, Mingzhi; Li, Yingrui; Yan, Zhixiang; Butcher, Lee M.; Sun, Jihua; Han, Xu; Chen, Quan; zhang, Xiuqing; Wang, Jun

doi:10.1016/j.ymeth.2010.04.009

Cited by 166 publications

(127 citation statements)

References 23 publications

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“…Comparisons of affinity-based methylome mapping techniques are now beginning to appear (Li et al 2010). Here, a comparison of MBDCap-and MeDIP-based affinity capture strategies was performed, as well as a comparison of promoter tiling arrays and sequencing-based readouts.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of affinity-based genome-wide DNA methylation data: Effects of CpG density, amplification bias, and copy number variation

Robinson

Stirzaker²,

Statham³

et al. 2010

Genome Res.

113

103

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DNA methylation is an essential epigenetic modification that plays a key role associated with the regulation of gene expression during differentiation, but in disease states such as cancer, the DNA methylation landscape is often deregulated. There are now numerous technologies available to interrogate the DNA methylation status of CpG sites in a targeted or genome-wide fashion, but each method, due to intrinsic biases, potentially interrogates different fractions of the genome. In this study, we compare the affinity-purification of methylated DNA between two popular genome-wide techniques, methylated DNA immunoprecipitation (MeDIP) and methyl-CpG binding domain-based capture (MBDCap), and show that each technique operates in a different domain of the CpG density landscape. We explored the effect of whole-genome amplification and illustrate that it can reduce sensitivity for detecting DNA methylation in GC-rich regions of the genome. By using MBDCap, we compare and contrast microarray-and sequencing-based readouts and highlight the impact that copy number variation (CNV) can make in differential comparisons of methylomes. These studies reveal that the analysis of DNA methylation data and genome coverage is highly dependent on the method employed, and consideration must be made in light of the GC content, the extent of DNA amplification, and the copy number.

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Section: Discussionmentioning

confidence: 99%

“…Comparison studies for DNA methylation platforms are now starting to emerge (Li et al 2010). MeDIP uses an antibody to 5-methyl-cytosine, targeting single-stranded DNA (Weng et al 2009; Ruike et al 2010), while the MBDCap approach uses the methyl-CpG binding domain of the MBD2 protein to capture double-stranded DNA (Serre et al 2009).…”

mentioning

confidence: 99%

Evaluation of affinity-based genome-wide DNA methylation data: Effects of CpG density, amplification bias, and copy number variation

Robinson

Stirzaker²,

Statham³

et al. 2010

Genome Res.

113

103

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show abstract

“…The MBD2 protein specifically targets densely methylated CpGs 23 and does not target hydroxymethylated cytosines 23,24 thus sequencing MBD2-enriched DNA identifies methylated regions from the whole genome. Comparing the number of sequenced reads matching each region enabled us to identify methylation differences between cases and controls.…”

Section: Generation Of High Quality Genome-wide Mbd2-seq Profilesmentioning

confidence: 99%

Astrocytic abnormalities and global DNA methylation patterns in depression and suicide

et al. 2014

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Astrocytes are glial cells specific the central nervous system involved in numerous brain functions including regulation of synaptic transmission and of immune reactions. There is mounting evidence suggesting astrocytic dysfunction in psychopathologies such as major depression, however, little is known about the underlying etiological mechanisms. Here we report a two-stage study investigating genome-wide DNA methylation associated with astrocytic markers in depressive psychopathology. We first characterized prefrontal cortex samples from 121 individuals (76 who died during a depressive episode and 45 healthy controls) for the astrocytic markers GFAP, ALDH1L1, SOX9, GLUL, SCL1A3, GJA1, and GJB6. A subset of 22 cases with consistently downregulated astrocytic markers was then compared to 17 matched controls using MBD2-sequencing followed by validation with high resolution melting and bisulfite Sanger sequencing. With these data, we generated a genome-wide methylation map unique to altered astrocyte-associated depressive psychopathology. The map revealed differentially methylated regions (DMRs) between cases and controls, the majority of which displayed reduced methylation levels in cases. Among intragenic DMRs, GRIK2 and BEGAIN were the most significant, and also significantly correlated with genes expression. Cell sorted fractions were investigated and demonstrated an important non-neuronal contribution of methylation status in BEGAIN.Functional cell assays revealed promoter and enhancer-like properties in this region, which were markedly decreased by methylation. Furthermore, a large number of our DMRs overlapped known ENCODE identified regulatory elements. Taken together, our data indicate significant differences in the methylation patterns specific to astrocytic dysfunction associated with depressive psychopathology, providing a potential framework for better understanding this disease phenotype.

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“…Lastly, bisulfite sequencing (BS or Bs), a process where treatment of DNA with sodium bisulfite chemically converts unmethylated cytosines to uracil, has recently been coupled with next generation sequencing (NGS) approaches, e.g., whole genome sequencing, (Laird, 2010;Li et al, 2010) and also with RAD sequencing (BsRADseq) (Trucchi et al, 2016). NGS-based approaches have greatly increased the level of resolution of quantifying DNA methylation, and linking the patterns to the genome and gene regulation (Marsh et al, 2016).…”

Section: Measuring Dna Methylationmentioning

confidence: 99%

Ecological Epigenetics in Marine Metazoans

Hofmann

2017

Front. Mar. Sci.

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In this horizon scan article, I review the emerging area of ecological epigenetics in marine animals with studies of DNA methylation as the primary focus. Epigenetic mechanisms such as DNA methylation have the capacity to create rapid changes in phenotypic plasticity. Epigenetic modifications of DNA are mechanisms that modify gene expression, and may do so in marine animals in an environmentally-induced manner. Thus, changes in the transcriptome that are driven by DNA methylation in response to environmental change may be one process by which marine animals can respond to anthropogenic, environmental change. From a technical standpoint, assays to quantify levels of DNA methylation, and next-generation sequencing approaches are opening up new avenues of exploration, such as simultaneously profiling the transcriptome and the methylome. A horizon scan for this topic suggests that the use of epigenomics and other methods to quantify DNA methylation will likely reveal important mechanisms of response to rapid environmental change in marine metazoans.

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Whole genome DNA methylation analysis based on high throughput sequencing technology

Cited by 166 publications

References 23 publications

Evaluation of affinity-based genome-wide DNA methylation data: Effects of CpG density, amplification bias, and copy number variation

Evaluation of affinity-based genome-wide DNA methylation data: Effects of CpG density, amplification bias, and copy number variation

Astrocytic abnormalities and global DNA methylation patterns in depression and suicide

Ecological Epigenetics in Marine Metazoans

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