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DNA methylation and gene expression in Mimulus guttatus.

Colicchio JM, Miura F, Kelly JK, Ito T, Hileman LC - BMC Genomics (2015)

Bottom Line: Additionally, we find that DNA methylation is significantly depleted near gene transcriptional start sites, which may explain the recently discovered elevated rate of recombination in these same regions.Using a model-based approach, we demonstrate that methylation patterns are an important predictor of variation in gene expression.This model provides a novel approach for differential methylation analysis that generates distinct and testable hypotheses regarding gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence, KS, 66045, USA. Colicchio@ku.edu.

ABSTRACT

Background: The presence of methyl groups on cytosine nucleotides across an organism's genome (methylation) is a major regulator of genome stability, crossing over, and gene regulation. The capacity for DNA methylation to be altered by environmental conditions, and potentially passed between generations, makes it a prime candidate for transgenerational epigenetic inheritance. Here we conduct the first analysis of the Mimulus guttatus methylome, with a focus on the relationship between DNA methylation and gene expression.

Results: We present a whole genome methylome for the inbred line Iron Mountain 62 (IM62). DNA methylation varies across chromosomes, genomic regions, and genes. We develop a model that predicts gene expression based on DNA methylation (R(2) = 0.2). Post hoc analysis of this model confirms prior relationships, and identifies novel relationships between methylation and gene expression. Additionally, we find that DNA methylation is significantly depleted near gene transcriptional start sites, which may explain the recently discovered elevated rate of recombination in these same regions.

Conclusions: The establishment here of a reference methylome will be a useful resource for the continued advancement of M. guttatus as a model system. Using a model-based approach, we demonstrate that methylation patterns are an important predictor of variation in gene expression. This model provides a novel approach for differential methylation analysis that generates distinct and testable hypotheses regarding gene expression.

No MeSH data available.


Related in: MedlinePlus

DNA methylation around transcriptional start sites. Around gene start sites, and persisting into the first 500 base pairs of the gene body, we observe a significant drop in DNA methylation. For CG (p-value = 6.45 × 10−55), CHG (p = 3.38 × 10−100), and CHH (p = 4.61 × 10−308) methylation was significantly reduced in the first 500bp of the gene relative to the up-stream regions. Both CG (p = 3.55 × 10−138) and CHG (p = 4.04 × 10−11) methylation then significantly increases over the next 500 bp, while for CHH it continued to decline (p = 8.93 × 10−10)
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Fig8: DNA methylation around transcriptional start sites. Around gene start sites, and persisting into the first 500 base pairs of the gene body, we observe a significant drop in DNA methylation. For CG (p-value = 6.45 × 10−55), CHG (p = 3.38 × 10−100), and CHH (p = 4.61 × 10−308) methylation was significantly reduced in the first 500bp of the gene relative to the up-stream regions. Both CG (p = 3.55 × 10−138) and CHG (p = 4.04 × 10−11) methylation then significantly increases over the next 500 bp, while for CHH it continued to decline (p = 8.93 × 10−10)

Mentions: We looked for changes in methylation near gene transcription start sites. We found that CG, CHG, and CHH methylation all were significantly depleted at and around gene start sites (Fig. 8). This depletion, along with the negative interaction term between up-stream and gene body CG methylation on gene expression, points towards a role of methylation in epigenetically labeling coding genetic regions. Additionally, recent evidence has shown that in M. guttatus genetic recombination occurs at higher frequency near gene start sites. In other systems it has been shown that DNA methylation is negatively correlated with recombination [7], and it may be that decreased methylation at gene start sites is related to the increase in recombination.Fig. 8


DNA methylation and gene expression in Mimulus guttatus.

Colicchio JM, Miura F, Kelly JK, Ito T, Hileman LC - BMC Genomics (2015)

DNA methylation around transcriptional start sites. Around gene start sites, and persisting into the first 500 base pairs of the gene body, we observe a significant drop in DNA methylation. For CG (p-value = 6.45 × 10−55), CHG (p = 3.38 × 10−100), and CHH (p = 4.61 × 10−308) methylation was significantly reduced in the first 500bp of the gene relative to the up-stream regions. Both CG (p = 3.55 × 10−138) and CHG (p = 4.04 × 10−11) methylation then significantly increases over the next 500 bp, while for CHH it continued to decline (p = 8.93 × 10−10)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4492170&req=5

Fig8: DNA methylation around transcriptional start sites. Around gene start sites, and persisting into the first 500 base pairs of the gene body, we observe a significant drop in DNA methylation. For CG (p-value = 6.45 × 10−55), CHG (p = 3.38 × 10−100), and CHH (p = 4.61 × 10−308) methylation was significantly reduced in the first 500bp of the gene relative to the up-stream regions. Both CG (p = 3.55 × 10−138) and CHG (p = 4.04 × 10−11) methylation then significantly increases over the next 500 bp, while for CHH it continued to decline (p = 8.93 × 10−10)
Mentions: We looked for changes in methylation near gene transcription start sites. We found that CG, CHG, and CHH methylation all were significantly depleted at and around gene start sites (Fig. 8). This depletion, along with the negative interaction term between up-stream and gene body CG methylation on gene expression, points towards a role of methylation in epigenetically labeling coding genetic regions. Additionally, recent evidence has shown that in M. guttatus genetic recombination occurs at higher frequency near gene start sites. In other systems it has been shown that DNA methylation is negatively correlated with recombination [7], and it may be that decreased methylation at gene start sites is related to the increase in recombination.Fig. 8

Bottom Line: Additionally, we find that DNA methylation is significantly depleted near gene transcriptional start sites, which may explain the recently discovered elevated rate of recombination in these same regions.Using a model-based approach, we demonstrate that methylation patterns are an important predictor of variation in gene expression.This model provides a novel approach for differential methylation analysis that generates distinct and testable hypotheses regarding gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence, KS, 66045, USA. Colicchio@ku.edu.

ABSTRACT

Background: The presence of methyl groups on cytosine nucleotides across an organism's genome (methylation) is a major regulator of genome stability, crossing over, and gene regulation. The capacity for DNA methylation to be altered by environmental conditions, and potentially passed between generations, makes it a prime candidate for transgenerational epigenetic inheritance. Here we conduct the first analysis of the Mimulus guttatus methylome, with a focus on the relationship between DNA methylation and gene expression.

Results: We present a whole genome methylome for the inbred line Iron Mountain 62 (IM62). DNA methylation varies across chromosomes, genomic regions, and genes. We develop a model that predicts gene expression based on DNA methylation (R(2) = 0.2). Post hoc analysis of this model confirms prior relationships, and identifies novel relationships between methylation and gene expression. Additionally, we find that DNA methylation is significantly depleted near gene transcriptional start sites, which may explain the recently discovered elevated rate of recombination in these same regions.

Conclusions: The establishment here of a reference methylome will be a useful resource for the continued advancement of M. guttatus as a model system. Using a model-based approach, we demonstrate that methylation patterns are an important predictor of variation in gene expression. This model provides a novel approach for differential methylation analysis that generates distinct and testable hypotheses regarding gene expression.

No MeSH data available.


Related in: MedlinePlus