scholarly journals Genome-Wide DNA Methylation Changes of Perirenal Adipose Tissue in Rabbits Fed a High-Fat Diet

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2213
Author(s):  
Jiahao Shao ◽  
Xue Bai ◽  
Ting Pan ◽  
Yanhong Li ◽  
Xianbo Jia ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Enrichment Analysis ◽  
Epigenetic Mechanism ◽  
Pathway Enrichment Analysis ◽  
High Fat ◽  
Perirenal Adipose Tissue ◽  
Pathway Enrichment ◽  
Genome Wide

DNA methylation is an epigenetic mechanism that plays an important role in gene regulation without an altered DNA sequence. Previous studies have demonstrated that diet affects obesity by partially mediating DNA methylation. Our study investigated the genome-wide DNA methylation of perirenal adipose tissue in rabbits to identify the epigenetic changes of high-fat diet-mediated obesity. Two libraries were constructed pooling DNA of rabbits fed a standard normal diet (SND) and DNA of rabbits fed a high-fat diet (HFD). Differentially methylated regions (DMRs) were identified using the option of the sliding window method, and online software DAVID Bioinformatics Resources 6.7 was used to perform Gene Ontology (GO) terms and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis of DMRs-associated genes. A total of 12,230 DMRs were obtained, of which 2305 (1207 up-regulated, 1098 down-regulated) and 601 (368 up-regulated, 233 down-regulated) of identified DMRs were observed in the gene body and promoter regions, respectively. GO analysis revealed that the DMRs-associated genes were involved in developmental process (GO:0032502), cell differentiation (GO:0030154), and lipid binding (GO:0008289), and KEGG pathway enrichment analysis revealed the DMRs-associated genes were enriched in linoleic acid metabolism (KO00591), DNA replication (KO03030), and MAPK signaling pathway (KO04010). Our study further elucidates the possible functions of DMRs-associated genes in rabbit adipogenesis, contributing to the understanding of HFD-mediated obesity.

scholarly journals Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage

2018 ◽  
Vol 7 (5) ◽  
pp. 343-350 ◽  
Author(s):  
A. He ◽  
Y. Ning ◽  
Y. Wen ◽  
Y. Cai ◽  
K. Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Signalling Pathway ◽  
Pathway Enrichment Analysis ◽  
Osteoarthritic Cartilage ◽  
Pathway Enrichment ◽  
Genome Wide

Aim Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Patients and Methods Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results We identified 1265 differentially methylated genes, of which 145 are associated with significant changes in gene expression, such as DLX5, NCOR2 and AXIN2 (all p-values of both DNA methylation and mRNA expression < 0.05). Pathway enrichment analysis identified 26 OA-associated pathways, such as mitogen-activated protein kinase (MAPK) signalling pathway (p = 6.25 × 10-4), phosphatidylinositol (PI) signalling system (p = 4.38 × 10-3), hypoxia-inducible factor 1 (HIF-1) signalling pathway (p = 8.63 × 10-3 pantothenate and coenzyme A (CoA) biosynthesis (p = 0.017), ErbB signalling pathway (p = 0.024), inositol phosphate (IP) metabolism (p = 0.025), and calcium signalling pathway (p = 0.032). Conclusion We identified a group of genes and biological pathwayswhich were significantly different in both DNA methylation and mRNA expression profiles between patients with OA and controls. These results may provide new clues for clarifying the mechanisms involved in the development of OA. Cite this article: A. He, Y. Ning, Y. Wen, Y. Cai, K. Xu, Y. Cai, J. Han, L. Liu, Y. Du, X. Liang, P. Li, Q. Fan, J. Hao, X. Wang, X. Guo, T. Ma, F. Zhang. Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage. Bone Joint Res 2018;7:343–350. DOI: 10.1302/2046-3758.75.BJR-2017-0284.R1.

scholarly journals A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice

BMC Genomics ◽  
2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Madeline Rose Keleher ◽  
Rabab Zaidi ◽  
Lauren Hicks ◽  
Shyam Shah ◽  
Xiaoyun Xing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
High Fat Diet ◽  
High Fat ◽  
Genome Wide

scholarly journals Genome-wide hepatic DNA methylation changes in high-fat diet-induced obese mice

2017 ◽  
Vol 11 (2) ◽  
pp. 105 ◽  
Author(s):  
AhRam Yoon ◽  
Stephanie A. Tammen ◽  
Soyoung Park ◽  
Sung Nim Han ◽  
Sang-Woon Choi
Keyword(s):  
Dna Methylation ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Genome Wide

scholarly journals SNP-based pathway enrichment analysis for genome-wide association studies

2011 ◽  
Vol 12 (1) ◽  
pp. 99 ◽  
Author(s):  
Lingjie Weng ◽  
Fabio Macciardi ◽  
Aravind Subramanian ◽  
Guia Guffanti ◽  
Steven G Potkin ◽  
...  
Keyword(s):  
Association Studies ◽  
Enrichment Analysis ◽  
Genome Wide Association ◽  
Pathway Enrichment Analysis ◽  
Genome Wide Association Studies ◽  
Pathway Enrichment ◽  
Genome Wide

scholarly journals MON-708 Characterizing DNA Methylation Signatures in Adipose Tissue from Metabolic Impaired Asymptomatic Individuals

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Fabiola Escalante-Araiza ◽  
Francisco Barajas-Olmos ◽  
Angélica Martínez-Hernández ◽  
Eira Huerta-Ávila ◽  
Vanessa-Giselle Peschard ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Enrichment Analysis ◽  
B Value ◽  
Pathway Enrichment Analysis ◽  
Overlapping Genes ◽  
Global Epidemic ◽  
Cpg Sites ◽  
Asymptomatic Individuals ◽  
Group B

Abstract Obesity remains as a global epidemic characterized by progressive metabolic dysregulation in glucose homeostasis. Along with a genetic association in the development of T2D, epigenetic regulation has been suggested as a significant contributor in altered gene expression. Recent studies have described DNA methylation changes in insulin-sensitive tissues involved in T2D pathogenesis, however epigenetic dynamics on early stages to metabolic alterations is still unclear. We investigated potential DNA methylation signatures in 34 asymptomatic individuals from the GEMM family study. We compared differentially methylated CpG sites (DMC: B value&gt;0 and delta Beta &gt;|10%|; Infinium EPIC array) from subcutaneous adipose tissue (SCAT) in different groups of individuals according to BMI (kg/m2) and HbA1c (%) levels as follow: Group A Control (C): n=9, 22.0±1.9 kg/m2, 4.8±0.3%; Group B Overweight (OW) with normal HbA1c: n=6, 27.8±1.6 kg/m2, 5±0.2%; Group C Obese (OB) with normal HbA1c: n=6, 34.6±4.2 kg/m2, 5.2±0.2%; Group D Prediabetes (PD): n=7, 31.1±5.7 kg/m2, 5.9±0.2% and Group E T2D: n=6, 30.6±7.3 kg/m2, 7.2±0.9%. We found 43 overlapping genes with shared pathways in all groups, mainly those related to metabolism and adipogenesis. We also documented particular altered methylated genes, in each group (OW: 386, OB:1005, PD:76 and T2D:189). Pathway enrichment analysis in OB and T2D was mainly related to glucose metabolism, while in OW and PD was NOTCH signaling. All groups displayed a consistent hypermethylation in RARA, ESR1 and NCOR2, well known genes involved in lipid metabolism. Additionally, we describe for the first time, a progression toward hypomethylation in ARHGAP15 and MTAP, related with an impaired metabolic status. Otherwise, analysis of overlapping CpG sites revealed a consistently hypermethylated state in OW (86.42%), OB (86.48%) and PD (51.72%), in contrast with the hypomethylation state (56.3%) observed in the T2D group, previously observed elsewhere (1). In conclusion, comparison of methylation in SCAT obtained from OW, OB, PD and T2D individuals, display potential pathways and DMC signatures specific in each group. Common novel overlapping genes in global DNA methylation profiles of SCAT, were also observed. Reference: (1) Barajas-Olmos et al., BMC Med Genet. 2018 Feb 21;19(1):1-8. Nothing to Disclose: FE, FB, AM, EH, GEMM, ER, RB, LO.

scholarly journals Genome-wide identification and characterization of perirenal adipose tissue microRNAs in rabbits fed a high-fat diet

2021 ◽  
Author(s):  
Jie Wang ◽  
Jiahao Shao ◽  
Yanhong Li ◽  
Mauricio A Elzo ◽  
Xianbo Jia ◽  
...  
Keyword(s):  
Intermediate Filament ◽  
High Fat Diet ◽  
Metabolic Regulation ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Normal Diet ◽  
Pathway Enrichment Analysis ◽  
High Fat ◽  
Cytoskeleton Organization ◽  
Kegg Pathways

MicroRNAs (miRNAs) are a class of endogenous single-stranded RNA molecules that play an important role in gene regulation in animals by pairing with target gene mRNA. Extensive evidence shows that miRNAs are key players in metabolic regulation and the development of obesity. However, the systemic understanding of miRNAs in the adipogenesis of obese rabbit need further investigate. Here, seven small RNA libraries from rabbits fed either a standard normal diet (SND; n = 3) or high-fat diet (HFD; n = 4) were constructed and sequenced. Differentially expressed (DE) miRNAs were identified using the edgeR data analysis package from R. Software miRanda and RNAhybrid were used to predict the target genes of miRNAs. To further explore the functions of DE miRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. A total of 81,449,996 clean reads were obtained from the seven libraries, of which, 52 known DE miRNAs (24 up-regulated, 28 down-regulated) and 31 novel DE miRNAs (14 up-regulated, 17 down-regulated) were identified. GO enrichment analysis revealed that the DE miRNAs target genes were involved in intermediate filament cytoskeleton organization, intermediate filament-based process, and alpha-tubulin binding. DE miRNAs were involved in p53 signaling, linoleic acid metabolism, and other adipogenesis-related KEGG pathways. Our study further elucidates the possible functions of DE miRNAs in rabbit adipogenesis, contributing to the understanding of rabbit obesity.

scholarly journals Integrative genomics analysis of various omics data and networks identify risk genes and variants vulnerable to childhood-onset asthma

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiuqing Ma ◽  
Peilan Wang ◽  
Guobing Xu ◽  
Fang Yu ◽  
Yunlong Ma
Keyword(s):  
Gene Expression ◽  
Genetic Variants ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Integrative Genomics ◽  
Ppi Network ◽  
Childhood Onset ◽  
Pathway Enrichment ◽  
Asthma Risk ◽  
Genome Wide

Abstract Background Childhood-onset asthma is highly affected by genetic components. In recent years, many genome-wide association studies (GWAS) have reported a large group of genetic variants and susceptible genes associated with asthma-related phenotypes including childhood-onset asthma. However, the regulatory mechanisms of these genetic variants for childhood-onset asthma susceptibility remain largely unknown. Methods In the current investigation, we conducted a two-stage designed Sherlock-based integrative genomics analysis to explore the cis- and/or trans-regulatory effects of genome-wide SNPs on gene expression as well as childhood-onset asthma risk through incorporating a large-scale GWAS data (N = 314,633) and two independent expression quantitative trait loci (eQTL) datasets (N = 1890). Furthermore, we applied various bioinformatics analyses, including MAGMA gene-based analysis, pathway enrichment analysis, drug/disease-based enrichment analysis, computer-based permutation analysis, PPI network analysis, gene co-expression analysis and differential gene expression analysis, to prioritize susceptible genes associated with childhood-onset asthma. Results Based on comprehensive genomics analyses, we found 31 genes with multiple eSNPs to be convincing candidates for childhood-onset asthma risk; such as, PSMB9 (cis-rs4148882 and cis-rs2071534) and TAP2 (cis-rs9267798, cis-rs4148882, cis-rs241456, and trans-10,447,456). These 31 genes were functionally interacted with each other in our PPI network analysis. Our pathway enrichment analysis showed that numerous KEGG pathways including antigen processing and presentation, type I diabetes mellitus, and asthma were significantly enriched to involve in childhood-onset asthma risk. The co-expression patterns among 31 genes were remarkably altered according to asthma status, and 25 of 31 genes (25/31 = 80.65%) showed significantly or suggestively differential expression between asthma group and control group. Conclusions We provide strong evidence to highlight 31 candidate genes for childhood-onset asthma risk, and offer a new insight into the genetic pathogenesis of childhood-onset asthma.

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