Genome-Wide DNA Methylation Profile Reveals Potential Therapeutic Targets at the Late Stage of Knee Osteoarthritis

2020 ◽  
Author(s):  
Hongyan Shen ◽  
Jie Long ◽  
Mingmei Zhang ◽  
Xing Chen ◽  
Tao Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Knee Osteoarthritis ◽  
Late Stage ◽  
Methylation Profile ◽  
Functional Enrichment ◽  
Intact Group ◽  
Knee Oa ◽  
Genome Wide ◽  
A Genome ◽  
Dna Methylation Profile

Abstract Background: The aim of this study was to use the latest BeadChip technology to obtain a genome-wide DNA methylation profile for cartilage from patients with primary knee osteoarthritis (OA), providing the first comprehensive description of DNA methylation changes in advanced knee OA. Methods: Cartilage tissues were taken from patients after total knee arthroplasty and were divided into eroded group and intact group according to the cartilage status. The genome-wide DNA methylation profile was obtained using the Infinium MethylationEPIC BeadChip kit, which enables the analysis of >850,000 CpG sites. Comparisons of the two groups were performed to identify differentially methylated (DM) probes (DMPs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied to the functional annotation clustering of the DM genes. Results: There was significant differential methylation between the two groups, and a total of 16,776 DMPs covering approximately 6,700 genes were identified, 92% of which were hypomethylated. Functional enrichment results revealed that the DM genes were significantly enriched for the extracellular matrix (ECM) proteins, cell adhesion molecules (CAM) and proteins in some inflammatory response pathways, especially the PI3K/Akt signalling pathway. Six genes including RNF43, SEMA4D, F11R, PKN1, FLT-1 and PTPN11 may be the potential biomarkers for OA.Conclusion: Our data demonstrate the epigenetic dysregulation of many genes and pathways in the late stage of knee OA that appear to be involved in potential aetiological mechanisms of OA. DM genes closely associated with OA may become targets for treatment and may open new avenues for further research in the field.

scholarly journals Methylome and transcriptome analyses of soybean response to bean pyralid larvae

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wei-Ying Zeng ◽  
Yu-Rong Tan ◽  
Sheng-Feng Long ◽  
Zu-Dong Sun ◽  
Zhen-Guang Lai ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Protein Biosynthesis ◽  
Cell Structure ◽  
Methylation Profile ◽  
Primary Metabolism ◽  
Global Methylation ◽  
Genome Wide ◽  
Differentially Methylated Genes ◽  
Dna Methylation Profile ◽  
Soybean Resistance

Abstract Background Bean pyralid is one of the major leaf-feeding insects that affect soybean crops. DNA methylation can control the networks of gene expressions, and it plays an important role in responses to biotic stress. However, at present the genome-wide DNA methylation profile of the soybean resistance to bean pyralid has not been reported so far. Results Using whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq), we analyzed the highly resistant material (Gantai-2-2, HRK) and highly susceptible material (Wan82–178, HSK), under bean pyralid larvae feeding 0 h and 48 h, to clarify the molecular mechanism of the soybean resistance and explore its insect-resistant genes. We identified 2194, 6872, 39,704 and 40,018 differentially methylated regions (DMRs), as well as 497, 1594, 9596 and 9554 differentially methylated genes (DMGs) in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48 comparisons, respectively. Through the analysis of global methylation and transcription, 265 differentially expressed genes (DEGs) were negatively correlated with DMGs, there were 34, 49, 141 and 116 negatively correlated genes in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48, respectively. The MapMan cluster analysis showed that 114 negatively correlated genes were clustered in 24 pathways, such as protein biosynthesis and modification; primary metabolism; secondary metabolism; cell cycle, cell structure and component; RNA biosynthesis and processing, and so on. Moreover, CRK40; CRK62; STK; MAPK9; L-type lectin-domain containing receptor kinase VIII.2; CesA; CSI1; fimbrin-1; KIN-14B; KIN-14 N; KIN-4A; cytochrome P450 81E8; BEE1; ERF; bHLH25; bHLH79; GATA26, were likely regulatory genes involved in the soybean responses to bean pyralid larvae. Finally, 5 DMRs were further validated that the genome-wide DNA data were reliable through PS-PCR and 5 DEGs were confirmed the relationship between DNA methylation and gene expression by qRT-PCR. The results showed an excellent agreement with deep sequencing. Conclusions Genome-wide DNA methylation profile of soybean response to bean pyralid was obtained for the first time. Several specific DMGs which participated in protein kinase, cell and organelle, flavonoid biosynthesis and transcription factor were further identified to be likely associated with soybean response to bean pyralid. Our data will provide better understanding of DNA methylation alteration and their potential role in soybean insect resistance.

scholarly journals Chicken cecal DNA methylome alteration in the response to Salmonella enterica serovar Enteritidis inoculation

2020 ◽  
Author(s):  
Yuanmei Wang ◽  
Liying Liu ◽  
Min Li ◽  
Lili Lin ◽  
Pengcheng Su ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Signaling Pathway ◽  
Salmonella Enterica ◽  
Methylation Profile ◽  
Control Group ◽  
Poultry Production ◽  
Salmonella Enterica Serovar Enteritidis ◽  
Genome Wide ◽  
Differentially Methylated Genes ◽  
Dna Methylation Profile

Abstract Background: Salmonella enterica serovar Enteritidis (SE) is one of the pathogenic bacteria, which affects poultry production and poses a severe threat to public health. Chicken meat and eggs are the main sources of human salmonellosis. DNA methylation is involved in regulatory processes including gene expression, chromatin structure and genomic imprinting. To understand the methylation regulation in the response to SE inoculation in chicken, the genome-wide DNA methylation profile following SE inoculation was analyzed through whole-genome bisulfite sequencing in the current study.Results: There were 185,362,463 clean reads and 126,098,724 unique reads in the control group, and 180,530,750 clean Reads and 126,782,896 unique reads in the inoculated group. The methylation density in the gene body was higher than that in the upstream and downstream regions of the gene. There were 8,946 differentially methylated genes (3,639 hypo-methylated genes, 5,307 hyper-methylated genes) obtained between inoculated and control groups. Methylated genes were mainly enriched in immune-related Gene Ontology (GO) terms and metabolic process terms. Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, FoxO signaling pathway, Wnt signaling pathway and several metabolism-related pathways were significantly enriched. The density of differentially methylated cytosines in miRNAs was the highest. HOX genes were widely methylated.Conclusions: The genome-wide DNA methylation profile in the response to SE inoculation in chicken was analyzed. SE inoculation promoted the DNA methylation in the chicken cecum and caused methylation alteration in immune- and metabolic- related genes. Wnt signal pathway, miRNAs and HOX gene family may play crucial roles in the methylation regulation of SE inoculation in chicken. The findings herein will deepen the understanding of epigenetic regulation in the response to SE inoculation in chicken.

scholarly journals Genome-wide DNA methylation profile of early-onset endometrial cancer: its correlation with genetic aberrations and comparison with late-onset endometrial cancer

2019 ◽  
Vol 40 (5) ◽  
pp. 611-623 ◽  
Author(s):  
Takeshi Makabe ◽  
Eri Arai ◽  
Takuro Hirano ◽  
Nanako Ito ◽  
Yukihiro Fukamachi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Endometrial Cancer ◽  
Early Onset ◽  
Late Onset ◽  
Methylation Profile ◽  
Cancer Tissue ◽  
Cpg Sites ◽  
Genome Wide ◽  
Dna Methylation Profile ◽  
Endometrioid Endometrial Cancer

Abstract The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among ‘transcriptional factors’. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.

scholarly journals Genome‐wide DNA methylation profile analysis in thoracic ossification of the ligamentum flavum

2020 ◽  
Vol 24 (15) ◽  
pp. 8753-8762
Author(s):  
Tianqi Fan ◽  
Xiangyu Meng ◽  
Chuiguo Sun ◽  
Xiaoxi Yang ◽  
Guanghui Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Ligamentum Flavum ◽  
Profile Analysis ◽  
Methylation Profile ◽  
Genome Wide ◽  
Dna Methylation Profile

scholarly journals Temperature-independent genome-wide DNA methylation profile in turbot post-embryonic development

2020 ◽  
Vol 88 ◽  
pp. 102483
Author(s):  
P. Suarez-Bregua ◽  
A. Pérez-Figueroa ◽  
J. Hernández-Urcera ◽  
P. Morán ◽  
J. Rotllant
Keyword(s):  
Dna Methylation ◽  
Embryonic Development ◽  
Methylation Profile ◽  
Genome Wide ◽  
Dna Methylation Profile

Genome-wide DNA methylation profile of prepubertal porcine testis

2018 ◽  
Vol 30 (2) ◽  
pp. 349 ◽  
Author(s):  
Xi Chen ◽  
Liu-Hong Shen ◽  
Li-Xuan Gui ◽  
Fang Yang ◽  
Jie Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
High Throughput Sequencing ◽  
Cpg Islands ◽  
Methylation Profile ◽  
Testis Development ◽  
Body Regions ◽  
Genome Wide ◽  
Dna Methylation Profile ◽  
Mammalian Testis ◽  
Porcine Testis

The biological structure and function of the mammalian testis undergo important developmental changes during prepuberty and DNA methylation is dynamically regulated during testis development. In this study, we generated the first genome-wide DNA methylation profile of prepubertal porcine testis using methyl-DNA immunoprecipitation (MeDIP) combined with high-throughput sequencing (MeDIP-seq). Over 190 million high-quality reads were generated, containing 43 642 CpG islands. There was an overall downtrend of methylation during development, which was clear in promoter regions but less so in gene-body regions. We also identified thousands of differentially methylated regions (DMRs) among the three prepubertal time points (1 month, T1; 2 months, T2; 3 months, T3), the majority of which showed decreasing methylation levels over time. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that many genes in the DMRs were linked with cell proliferation and some important pathways in porcine testis development. Our data suggest that DNA methylation plays an important role in prepubertal development of porcine testis, with an obvious downtrend of methylation levels from T1 to T3. Overall, our study provides a foundation for future studies and gives new insights into mammalian testis development.

scholarly journals The Genome-Wide DNA Methylation Profile of Peripheral Blood Is Not Systematically Changed by Short-Time Storage at Room Temperature

Epigenomes ◽  
2017 ◽  
Vol 1 (3) ◽  
pp. 23
Author(s):  
Nicklas Heine Staunstrup ◽  
Anna Starnawska ◽  
Mette Nyegaard ◽  
Anders Lade Nielsen ◽  
Anders Dupont Børglum ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Peripheral Blood ◽  
Room Temperature ◽  
Methylation Profile ◽  
Genome Wide ◽  
Dna Methylation Profile ◽  
Short Time
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