Abstract
Long intergenic noncoding RNAs (lincRNAs) are one of the major unexplored components of genomes. Here we re-analyzed a published methylated DNA immunoprecipitation sequencing (MeDIP-seq) dataset to characterize the DNA methylation pattern of pig lincRNA genes in adipose and muscle tissues. Our study showed that the methylation level of lincRNA genes was higher than that of mRNA genes, with similar trends observed in comparisons of the promoter, exon or intron regions. Different methylation pattern were observed across the transcription start sites (TSS) of lincRNA and protein-coding genes. Furthermore, an overlap was observed between many lincRNA genes and differentially methylated regions (DMRs) identified among different breeds of pigs, which show different fat contents, sexes and anatomic locations of tissues. We identify a lincRNA gene, linc-sscg3623, that displayed differential methylation levels in backfat between Min and Large White pigs at 60 and 120 days of age. We found that a demethylation process occurred between days 150 and 180 in the Min and Large White pigs, which was followed by remethylation between days 180 and 210. These results contribute to our understanding of the domestication of domestic animals and identify lincRNA genes involved in adipogenesis and muscle development.
Highlights
Show varying performance in adipose and lean meat production
Several studies have indicated that DNA methylation plays important roles in stem cell differentiation[24] and embryonic development[25], and that alternations in DNA methylation are associated with disease[26]
To compare DNA methylation pattern between lincRNA and protein-coding genes, we focused on the genomic regions consisting of their promoters and their gene bodies, and found that lincRNA genes have higher DNA methylation levels than protein-coding genes despite lincRNA genes having similar GC content and CpGo/e as protein-coding genes
Summary
Global patterns of DNA methylation in lncRNA genes. In our previous study, we found pig lincRNA genes have several characteristics which differ from those of mRNA genes such as their length, number of exons and level of expression[16]. The methylation levels of the lincRNA genomic regions were significantly higher than that for the mRNA genes (Kolmogorov-Smirnov test, P = 2.621 × 10−10, Fig. 1a), which indicates that there is a differential methylation pattern between protein-coding and lincRNA genes. We found similar methylation patterns in male and female, for both adipose and muscle tissues, with the methylation level across the TSS of lincRNA genes being higher than for protein-coding genes (Fig. 2). Both lincRNA and protein-coding genes showed higher GC content and CpGo/e near their TSSs (Fig. 3) When this result is combined with our observations on the methylation levels around TSS, we concluded that the differential methylation pattern seen between lincRNA and mRNA genes is most likely due to differential regulation of DNA methylation, rather than nucleotide composition. These observations suggest that linc-sscg3623 may show differences in expression level between differential breeds or development stages and affect adipogenesis
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