Genome-wide DNA methylation profiles provide insight into epigenetic regulation of red and white muscle development in Chinese perch Siniperca chuatsi

Author(s):  
Yaxiong Pan ◽  
Lin Chen ◽  
Jia Cheng ◽  
Xin Zhu ◽  
Ping Wu ◽  
...  
2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Ieva Rauluseviciute ◽  
Finn Drabløs ◽  
Morten Beck Rye

Abstract Background Prostate cancer (PCa) has the highest incidence rates of cancers in men in western countries. Unlike several other types of cancer, PCa has few genetic drivers, which has led researchers to look for additional epigenetic and transcriptomic contributors to PCa development and progression. Especially datasets on DNA methylation, the most commonly studied epigenetic marker, have recently been measured and analysed in several PCa patient cohorts. DNA methylation is most commonly associated with downregulation of gene expression. However, positive associations of DNA methylation to gene expression have also been reported, suggesting a more diverse mechanism of epigenetic regulation. Such additional complexity could have important implications for understanding prostate cancer development but has not been studied at a genome-wide scale. Results In this study, we have compared three sets of genome-wide single-site DNA methylation data from 870 PCa and normal tissue samples with multi-cohort gene expression data from 1117 samples, including 532 samples where DNA methylation and gene expression have been measured on the exact same samples. Genes were classified according to their corresponding methylation and expression profiles. A large group of hypermethylated genes was robustly associated with increased gene expression (UPUP group) in all three methylation datasets. These genes demonstrated distinct patterns of correlation between DNA methylation and gene expression compared to the genes showing the canonical negative association between methylation and expression (UPDOWN group). This indicates a more diversified role of DNA methylation in regulating gene expression than previously appreciated. Moreover, UPUP and UPDOWN genes were associated with different compartments — UPUP genes were related to the structures in nucleus, while UPDOWN genes were linked to extracellular features. Conclusion We identified a robust association between hypermethylation and upregulation of gene expression when comparing samples from prostate cancer and normal tissue. These results challenge the classical view where DNA methylation is always associated with suppression of gene expression, which underlines the importance of considering corresponding expression data when assessing the downstream regulatory effect of DNA methylation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jinshan Ran ◽  
Jingjing Li ◽  
Lingqian Yin ◽  
Donghao Zhang ◽  
Chunlin Yu ◽  
...  

DNA methylation is a key epigenetic mechanism involved in embryonic muscle development and plays an important role in early muscle development. In this study, we sought to investigate the effects of genome-wide DNA methylation by combining the expression profiles of the chicken embryonic muscle. Genome-wide DNA methylation maps and transcriptomes of muscle tissues collected from different embryonic development points (E7, E11, E17, and D1) were used for whole-genome bisulfite sequencing (WGBS) and RNA sequencing, respectively. We found that the differentially methylated genes (DMGs) were significantly associated with muscle organ development, regulation of skeletal muscle satellite cell proliferation, and actin filament depolymerization. Furthermore, genes TBX1, MEF2D, SPEG, CFL2, and TWF2 were strongly correlated with the methylation-caused expression switch. Therefore, we chose the CFL2 gene to explore its function in skeletal muscle satellite cells, and the in vitro experiments showed that CFL2 acts as a negative regulator of chicken skeletal muscle satellite cell proliferation and can induce cell apoptosis. These results provide valuable data for future genome and epigenome studies of chicken skeletal muscle and may help reveal the molecular mechanisms of potential economic traits.


2019 ◽  
Author(s):  
Jingru Zhang ◽  
Shuxian Wu ◽  
Yajuan Huang ◽  
Haishen Wen ◽  
Meizhao Zhang ◽  
...  

AbstractDNA methylation is an important epigenetic modification in vertebrate and is essential for epigenetic gene regulation in skeletal muscle development. We showed the genome-wide DNA methylation profile in skeletal muscle tissue of larval 7dph (JP1), juvenile 90dph (JP2), adult female 24 months (JP3) and adult male 24 months (JP4) Japanese flounder. The distribution and levels of methylated DNA within genomic features (1stexons, gene body, introns, TSS200, TSS1500 and intergenic) show different developmental landscapes. We also successfully identified differentially methylated regions (DMRs) and different methylated genes (DMGs) through a comparative analysis, indicating that DMR in gene body, intron and intergenic regions were more compared to other regions of all DNA elements. A gene ontology analysis indicated that the DMGs were mainly related to regulation of skeletal muscle fiber development process, Axon guidance, Adherens junction, and some ATPase activity. Methylome and transcriptome clearly revealed a exhibit a negative correlation. And integration analysis revealed a total of 425, 398 and 429 negatively correlated genes with methylation in the JP2_VS_JP1, JP3_VS_JP1 and JP4_VS_JP1 comparison groups, respectively. And these genes were functionally associated with pathways including Adherens junction, Axon guidance, Focal adhesion, cell junctions, Actin cytoskeleton and Wnt signaling pathways. In addition, we validated the MethylRAD results by bisulfite sequencing PCR (BSP) in some of the differentially methylated skeletal muscle growth-related genes (Myod1, Six1 and Ctnnb1). In this study, we have generated the genome-wide profile of methylome and transcriptome in Japanese flounder for the first time, and our results bring new insights into the epigenetic regulation of developmental processes in Japanese flounder. This study contributes to the knowledge on epigenetics in vertebrates.Author summaryEpigenetic mechanisms like DNA methylation have recently reported as vital regulators of some species skeletal muscle development through the control of genes related to growth. To date, although genome-wide DNA methylation profiles of many organisms have been reported and the Japanese flounder reference genome and whole transcriptome data are publically available, the methylation pattern of Japanese flounder skeletal muscle tissue remains minimally studied and the global DNA methylation data are yet to be known. Here we investigated the genome-wide DNA methylation patterns in Japanese flounder, throughout its development. These findings help to enrich research in molecular and developmental biology in vertebrates.


AGROFOR ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Barbora OLŠANSKÁ ◽  
Radovan KASARDA ◽  
Kristína LEHOCKÁ ◽  
Nina MORAVČÍKOVÁ

The presented study provides a genome-wide scan of selection signals in cattle by principal component analysis (PCA). The aim was to identify SNP affected by intensive selection based on package PCAdapt implemented under software R. This analysis provided insight into the association between the SNP frequencies related to population differentiation. The four cattle populations were involved in the analysis (Slovak Spotted cattle, Ayrshire, Swiss Simmental and Holstein) with overall 272 of genotyped individuals. After applying quality control, the final dataset consisted of 35 675 SNPs, with an overall length of 2496.14 Mb and average space between adjacent SNP 70.03 ± 76.1 kb. After performing PCA analysis, the uniqueness of the breeds was revealed. On the other hand, a close genetic relationship and eleven SNPs affected by selection were found, with a position close to 162 genes involved in the various biological processes. The majority of genes were involved in the positive regulation of adenylate cyclase activity, embryo development and somatic diversification of immune receptors via somatic mutation. Several candidate genes for genetic control of the immune system (DNAJB9), muscle development (SEPT7, TRIM32, ROCK1, NRAP, PZDZ8, HSPA12A and FGFR2), milk production (SOCS5, CD46), reproduction (LHCGR, EEPD1, FSHR) and coat colour (KIT) were identified. Our results provide insights into the regions of the genome affected by the intensive selection of analysed cattle populations.


2019 ◽  
Vol 31 (1) ◽  
pp. 126
Author(s):  
J. E. Duan ◽  
Z. Jiang ◽  
F. Alqahtani ◽  
I. Mandoiu ◽  
H. Dong ◽  
...  

Dynamic changes in DNA methylation are crucial in the epigenetic regulation of mammalian embryogenesis. Global DNA methylation studies in the bovine, however, remain mostly at the immunostaining level. We adopted the single-cell whole-genome bisulfite sequencing method to characterise stage-specific genome-wide DNA methylation in bovine sperm, individual oocytes derived invivo and invitro, and invivo-developed embryos at the 2-, 4-, 8-, and 16-cell stages. This method allowed us to theoretically cover all CpG sites in the genome using a limited number of cells from single embryos. Pools of 20 sperm were selected from a bull with proven fertility. Single oocytes (n=6) and embryos (n=4 per stage) were collected from Holstein cows (n=10). Single-cell whole-genome bisulfite sequencing libraries were prepared and sequenced using the Illumina HiSEqn 4000 platform (Illumina, San Diego, CA, USA). Sequencing reads were filtered and aligned to the bovine reference genome (UMD 3.1.1) using Bismark (Krueger and Andrews 2011Bioinformatics27, 1571-1572, DOI: 10.1093/bioinformatics/btr167).A 300-bp tile-based method was applied to bin the genome into consecutive windows to facilitate comparison across samples. The DNA methylation level was calculated as the fraction of read counts of the total number of cytosines (methylated) in the total read counts of reported cytosines and thymines (methylated and unmethylated), only if more than 3 CpG sites were covered in this tile. Gamete-specific differentially methylated regions were identified when DNA methylation levels were greater than 75% in one type of gamete and less than 25% in the other with false discovery rate-corrected Fisher’s exact test P-values of less than 0.05. The major wave of genome-wide DNA demethylation was complete at the 8-cell stage when de novo methylation became prominent. Sperm and oocytes had numerous differentially methylated regions that were enriched in intergenic regions. Differentially methylated regions were also identified between invivo- and invitro-matured oocytes. Moreover, X chromosome methylation followed the global dynamic patterns. Virtually no (less than 1.5%) DNA methylation was found in mitochondrial DNA. Finally, using our RNA sequencing data generated from the same developmental stages (Jiang et al. 2014 BMC Genomics 15, 756; DOI: 10.1186/1471-2164-15-756), we revealed an inverse correlation between gene expression and promoter methylation. Our study provides the first fully comprehensive analysis of the global dynamics of DNA methylation in bovine gametes and single early embryos using single-cell whole-genome bisulfite sequencing. These data provide insights into the critical features of the methylome of bovine embryos and serve as an important reference for embryos produced by assisted reproduction, such as IVF and cloning, and a model for human early embryo epigenetic regulation.


Gene ◽  
2018 ◽  
Vol 642 ◽  
pp. 522-532 ◽  
Author(s):  
Long Jin ◽  
Ke Mao ◽  
Jing Li ◽  
Wenyao Huang ◽  
Tiandong Che ◽  
...  

Author(s):  
Abhijeet Roy

Type 2 Diabetes is one of the major public health issues and a complex metabolic disorder strongly associated with genetic predisposition influenced by environmental factors and epigenetic regulation. This review paper illustrated the role of epigenetics in the pathogenesis, progression, and detection of Type 2 Diabetes. A review study was performed for the articles published in English from 2000-2019 using Pub Med, and Google Scholar databases. Main underlining mechanisms of Type 2 Diabetes were identified; insulin resistance in the peripheral tissue, and disintegrate insulin secretion. Genome Wide Association Studies suggested that epigenetic regulation such as DNA methylation, Histone modification, Non-coding RNA, microRNA is strongly related with the development of Type 2 Diabetes. Altered DNA methylation patterns in pancreatic islets, skeletal muscle, adipose tissue, from diabetic subjects compare to normal subjects was also found. Other risk factors like; obesity, age, gender, impaired glucose tolerance, periconception and intrauterine environment may also have been linked with the possibilities of epigenetic changes. Epigenetics plays a crucial role by modifying the gene expression and establish a relationship between the environment and genetic factors. Understanding the epigenetic mechanisms contributing to the development of Type 2 Diabetes is still limited.


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