Abstract
DNA methylation, the most widely studied and most well-understood epigenetic modification, has been reported to play crucial roles in diverse processes. Although it has been found that DNA methylation can modulate the expression of immune-related genes in teleosts, a systemic analysis of epigenetic regulation on teleost immunity has rarely been performed. In this research, we employed whole-genome bisulfite sequencing to investigate the genome-wide DNA methylation profiles in select disease-resistant Cynoglossus semilaevis (DR-CS, family 14L006) and disease-susceptible C. semilaevis (DS-CS, family 14L104) against Vibrio harveyi infection. The results showed that following selective breeding, DR-CS had higher DNA methylation levels and different DNA methylation patterns, with 3,311 differentially methylated regions and 6,456 differentially methylated genes. Combining these data with the corresponding transcriptome data, we identified several immune-related genes that exhibited differential expression levels that were modulated by DNA methylation. Specifically, DNA methylation of tumor necrosis factor–like and lipopolysaccharide-binding protein-like was significantly correlated with their expression and significantly contributed to the disease resistance of the selected C. semilaevis family. In conclusion, we suggest that artificial selection for disease resistance in Chinese tongue sole causes changes in DNA methylation levels in important immune-related genes and that these epigenetic changes are potentially involved in multiple immune responses in Chinese tongue sole.
Highlights
Epigenetic modifications, which are influenced by external environmental factors and predetermined inherited programs, induce changes in gene activity without altering the underlying DNA sequence (Jablonka and Lamb, 2002; Long et al, 2014)
Among the detected methylation sites, the methylated Cs (mC) percentage of reference genomic cytosines was 4.44% and 3.38% for DR-CS and DS-CS, respectively; mCG sites accounted for 43.12% and 32.82% of DR-CS and DS-CS; and mCHG and mCHH sites accounted for 0.12% and 0.09% of DR-CS and DS-CS (Supplementary Table S3)
We provide the first comprehensive investigation of the DNA methylation and transcriptome relationships underlying the differences between V. harveyi-resistant and -susceptible Chinese tongue sole, providing insights into the role of epigenetics in the regulation of bony fish immunity
Summary
Epigenetic modifications, which are influenced by external environmental factors and predetermined inherited programs, induce changes in gene activity without altering the underlying DNA sequence (Jablonka and Lamb, 2002; Long et al, 2014). DNA methylation, the most widely and well-understood type of epigenetic modification, has been reported to play crucial roles in diverse. Epigenetic changes, which mainly alter DNA methylation profiles, have been implicated in various types of cancers. Hypermethylation of CpG islands in the promoter region results in transcriptional silencing of tumor suppressor genes, whereas hypomethylation leads to oncogene activation in many cancers (Baylin and Jones, 2011; Esteller, 2011; Rodríguez-Paredes and Esteller, 2011; Chatterjee and Vinson, 2012). Methylation has important functions in tumor initiation and progression, and changes in methylation have been used as potential biomarkers for the early detection of cancers (Meng et al, 2012; Farkas et al, 2013; Guo et al, 2015; Vedeld et al, 2015)
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