Gene expression and nucleotide composition are associated with genic methylation level in Oryza sativa

Abstract

Background: The methylation of cytosines at CpG dinucleotides, which plays an important role in gene expression regulation, is one of the most studied epigenetic modifications. Thus far, the detection of DNA methylation has been determined mostly by experimental methods, which are not only prone to bench effects and artifacts but are also time-consuming, expensive, and cannot be easily scaled up to many samples. It is therefore useful to develop computational prediction methods for DNA methylation. Our previous studies highlighted the existence of correlations between the GC content of the third codon position (GC₃), methylation, and gene expression. We thus designed a model to predict methylation in Oryza sativa based on genomic sequence features and gene expression data.

Results: We first derive equations to describe the relationship between gene methylation levels, GC₃, expression, length, and other gene compositional features. We next assess gene compositional features involving sixmers and their association with methylation levels and other gene level properties. By applying our sixmer-based approach on rice gene expression data we show that it can accurately predict methylation (Pearson's correlation coefficient r = 0.79) for the majority (79%) of the genes. Matlab code with our model is included.

Conclusions: Gene expression variation can be used as predictors of gene methylation levels.

Figure 1

Distribution of gene-body methylation.

Figure 2

Log-methylation vs. GC ₃ .

Figure 3

Gene methylation levels estimated from sixmers (x-axis) and the gene methylation level obtained from experimental data (after moving average smoothing). An exponential fitting is shown in red.

Figure 4

A flow chart of the proposed algorithm to calculate methylation from gene expression data (left to right). Calculations marked in black arrows are carried once for all genes, whereas calculation marked in green are carried for each specific gene.