Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs

BMC Genomics

Mingzhou Li⁵  Xuewei Li⁵  Jinyong Wang¹  Li Zhu⁵  An’an Jiang⁵  Junfang Shen²  Bangsheng Zhong⁵  Wei Li⁵  Yihui Liu⁵  Yanmei Xie⁵  Lu Bai⁵  Hongmei Wang⁵  Lei Chen¹  Ping’er Lou⁵  Yudong Xia³  Zhi Jiang⁴  Long Jin⁵ 

[1] Chongqing Academy of Animal Science, Chongqing 402460, China;BGI-Tech, BGI-Shenzhen, Shenzhen 518083, China;E-GENE, Shenzhen, Guangdong 518173, China;Novogene Bioinformatics Institute, Beijing 100083, China;Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Ya’an, Sichuan 625014, China

关键词: DNMTs;    MeDIP-seq;    Aging;    Pig;    Skeletal muscle;    DNA methylation;   

Others  :  1216296
DOI  :  10.1186/1471-2164-15-653

 received in 2014-05-01, accepted in 2014-07-31,  发布年份 2014

【 摘 要 】

Background

Age-related physiological, biochemical and functional changes in mammalian skeletal muscle have been shown to begin at the mid-point of the lifespan. However, the underlying changes in DNA methylation that occur during this turning point of the muscle aging process have not been clarified. To explore age-related genomic methylation changes in skeletal muscle, we employed young (0.5 years old) and middle-aged (7 years old) pigs as models to survey genome-wide DNA methylation in the longissimus dorsi muscle using a methylated DNA immunoprecipitation sequencing approach.

Results

We observed a tendency toward a global loss of DNA methylation in the gene-body region of the skeletal muscle of the middle-aged pigs compared with the young group. We determined the genome-wide gene expression pattern in the longissimus dorsi muscle using microarray analysis and performed a correlation analysis using DMR (differentially methylated region)-mRNA pairs, and we found a significant negative correlation between the changes in methylation levels within gene bodies and gene expression. Furthermore, we identified numerous genes that show age-related methylation changes that are potentially involved in the aging process. The methylation status of these genes was confirmed using bisulfite sequencing PCR. The genes that exhibited a hypomethylated gene body in middle-aged pigs were over-represented in various proteolysis and protein catabolic processes, suggesting an important role for these genes in age-related muscle atrophy. In addition, genes associated with tumorigenesis exhibited aged-related differences in methylation and expression levels, suggesting an increased risk of disease associated with increased age.

Conclusions

This study provides a comprehensive analysis of genome-wide DNA methylation patterns in aging pig skeletal muscle. Our findings will serve as a valuable resource in aging studies, promoting the pig as a model organism for human aging research and accelerating the development of comparative animal models in aging research.

【 授权许可】

   
2014 Jin et al.; licensee BioMed Central Ltd.

【 图 表 】

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