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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 across the Mimulus guttatus genome. DNA methylation across the 14 Mimulus guttatus linkage groups (putative chromosomes) in all three sequence contexts: CG (red), CHG (green), and CHH (blue). Centromeric repeat densities, adapted from [45], are shown along the X-axis (darker bars indicate higher repeat density). Areas with higher repeat density tend to also have higher DNA methylation. A smoother line [67] was fit across 1kb methylation averages
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Fig2: DNA methylation across the Mimulus guttatus genome. DNA methylation across the 14 Mimulus guttatus linkage groups (putative chromosomes) in all three sequence contexts: CG (red), CHG (green), and CHH (blue). Centromeric repeat densities, adapted from [45], are shown along the X-axis (darker bars indicate higher repeat density). Areas with higher repeat density tend to also have higher DNA methylation. A smoother line [67] was fit across 1kb methylation averages

Mentions: Approximate positions of centromeres on M. guttatus chromosomes are given by the location and density of centromeric repeats [45]. We confirmed that regions of the genome with high levels of centromeric repeats also tended to have high CG, CHG, and CHH methylation (Fig. 2). We found that gene expression and gene body CG, CHG, CHH methylation varied significantly across chromosomes (log(expression): F13,17042 = 4.43, CG: F13,17042 = 10.85, CHG: F13,17042 = 19.07, CHH: F13,170423 = 6.10, p < 0.001)). Chromosomes that have on average higher levels of methylation tended to also have lower gene expression (Fig. 3). From this result, it is unclear whether certain chromosomes are constitutively more highly methylated and transcriptionally silenced, or whether throughout development epigenetic modification at a whole chromosome scale can change the relative expression of genes across entire chromosomes. It does appear that silenced chromosomes have a higher density of heterochromatic repeats, hinting that certain chromosomes may be condensed throughout development.Fig. 2


DNA methylation and gene expression in Mimulus guttatus.

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

DNA methylation across the Mimulus guttatus genome. DNA methylation across the 14 Mimulus guttatus linkage groups (putative chromosomes) in all three sequence contexts: CG (red), CHG (green), and CHH (blue). Centromeric repeat densities, adapted from [45], are shown along the X-axis (darker bars indicate higher repeat density). Areas with higher repeat density tend to also have higher DNA methylation. A smoother line [67] was fit across 1kb methylation averages
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: DNA methylation across the Mimulus guttatus genome. DNA methylation across the 14 Mimulus guttatus linkage groups (putative chromosomes) in all three sequence contexts: CG (red), CHG (green), and CHH (blue). Centromeric repeat densities, adapted from [45], are shown along the X-axis (darker bars indicate higher repeat density). Areas with higher repeat density tend to also have higher DNA methylation. A smoother line [67] was fit across 1kb methylation averages
Mentions: Approximate positions of centromeres on M. guttatus chromosomes are given by the location and density of centromeric repeats [45]. We confirmed that regions of the genome with high levels of centromeric repeats also tended to have high CG, CHG, and CHH methylation (Fig. 2). We found that gene expression and gene body CG, CHG, CHH methylation varied significantly across chromosomes (log(expression): F13,17042 = 4.43, CG: F13,17042 = 10.85, CHG: F13,17042 = 19.07, CHH: F13,170423 = 6.10, p < 0.001)). Chromosomes that have on average higher levels of methylation tended to also have lower gene expression (Fig. 3). From this result, it is unclear whether certain chromosomes are constitutively more highly methylated and transcriptionally silenced, or whether throughout development epigenetic modification at a whole chromosome scale can change the relative expression of genes across entire chromosomes. It does appear that silenced chromosomes have a higher density of heterochromatic repeats, hinting that certain chromosomes may be condensed throughout development.Fig. 2

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