Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model.
DNA methylation is known to be associated with cataracts. In this study, we used a mouse model and performed DNA methylation and transcriptome sequencing analyses to find epigenetic indicators for age-related cataracts (ARC). Anterior lens capsule membrane tissues from young and aged mice were analy...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0316766 |
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| author | Yuzhu Hu Dongmei Su Yue Zhang Yanjiang Fu Sijia Li Xiaoya Chen Xiao Zhang Shunfei Zheng Xu Ma Shanshan Hu |
| author_facet | Yuzhu Hu Dongmei Su Yue Zhang Yanjiang Fu Sijia Li Xiaoya Chen Xiao Zhang Shunfei Zheng Xu Ma Shanshan Hu |
| author_sort | Yuzhu Hu |
| collection | DOAJ |
| description | DNA methylation is known to be associated with cataracts. In this study, we used a mouse model and performed DNA methylation and transcriptome sequencing analyses to find epigenetic indicators for age-related cataracts (ARC). Anterior lens capsule membrane tissues from young and aged mice were analyzed by MethylRAD-seq to detect the genome-wide methylation of extracted DNA. The young and aged mice had 76,524 and 15,608 differentially methylated CCGG and CCWGG sites, respectively. The Pearson correlation analysis detected 109 and 33 differentially expressed genes (DEGs) with negative methylation at CCGG and CCWGG sites, respectively, in their promoter regions. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses showed that DEGs with abnormal methylation at CCGG sites were primarily associated with protein kinase C signaling (Akap12, Capzb), protein threonine kinase activity (Dmpk, Mapkapk3), and calcium signaling pathway (Slc25a4, Cacna1f), whereas DEGs with abnormal methylation at CCWGG sites were associated with ribosomal protein S6 kinase activity (Rps6ka3). These genes were validated by pyrosequencing methylation analysis. The results showed that the ARC group (aged mice) had lower Dmpk and Slc25a4 methylation levels and a higher Rps6ka3 methylation than the control group (young mice), which is consistent with the results of the joint analysis of differentially methylated and differentially expressed genes. In conclusion, we confirmed the genome-wide DNA methylation pattern and gene expression profile of ARC based on the mouse cataract model with aged mice. The identified methylation molecular markers have great potential for application in the future diagnosis and treatment of ARC. |
| format | Article |
| id | doaj-art-4d2fbe666f3544119a34106c68895278 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-4d2fbe666f3544119a34106c688952782025-02-05T05:31:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031676610.1371/journal.pone.0316766Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model.Yuzhu HuDongmei SuYue ZhangYanjiang FuSijia LiXiaoya ChenXiao ZhangShunfei ZhengXu MaShanshan HuDNA methylation is known to be associated with cataracts. In this study, we used a mouse model and performed DNA methylation and transcriptome sequencing analyses to find epigenetic indicators for age-related cataracts (ARC). Anterior lens capsule membrane tissues from young and aged mice were analyzed by MethylRAD-seq to detect the genome-wide methylation of extracted DNA. The young and aged mice had 76,524 and 15,608 differentially methylated CCGG and CCWGG sites, respectively. The Pearson correlation analysis detected 109 and 33 differentially expressed genes (DEGs) with negative methylation at CCGG and CCWGG sites, respectively, in their promoter regions. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses showed that DEGs with abnormal methylation at CCGG sites were primarily associated with protein kinase C signaling (Akap12, Capzb), protein threonine kinase activity (Dmpk, Mapkapk3), and calcium signaling pathway (Slc25a4, Cacna1f), whereas DEGs with abnormal methylation at CCWGG sites were associated with ribosomal protein S6 kinase activity (Rps6ka3). These genes were validated by pyrosequencing methylation analysis. The results showed that the ARC group (aged mice) had lower Dmpk and Slc25a4 methylation levels and a higher Rps6ka3 methylation than the control group (young mice), which is consistent with the results of the joint analysis of differentially methylated and differentially expressed genes. In conclusion, we confirmed the genome-wide DNA methylation pattern and gene expression profile of ARC based on the mouse cataract model with aged mice. The identified methylation molecular markers have great potential for application in the future diagnosis and treatment of ARC.https://doi.org/10.1371/journal.pone.0316766 |
| spellingShingle | Yuzhu Hu Dongmei Su Yue Zhang Yanjiang Fu Sijia Li Xiaoya Chen Xiao Zhang Shunfei Zheng Xu Ma Shanshan Hu Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model. PLoS ONE |
| title | Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model. |
| title_full | Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model. |
| title_fullStr | Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model. |
| title_full_unstemmed | Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model. |
| title_short | Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model. |
| title_sort | genome wide dna methylation and transcriptome sequencing analyses of lens tissue in an age related mouse cataract model |
| url | https://doi.org/10.1371/journal.pone.0316766 |
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