Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood

AbstractDNA methylation patterns are closely related to the chromatin structure, and its remodeling is considered an important mechanism in the control of gene transcription during cell differentiation. In rodent, several studies have related the possibility that multipotent mesenchymal stromal cells (MSCs) undergo cardiomyogenesis. However, it has not been completely elucidated if human adult stem cell exhibits true differentiation potential for a cardiac lineage. In this study, the action of the DNA methylation inhibitor 5-azacytidine (5-aza) was examined in human adipose tissue pericytes (hATPCs: 3G5+) regarding their possible capacity to induce myocytes in vitro. Real-Time PCR revealed that cells treated with 5-aza presented time-dependent decrease in the mRNA expression of α-cardiac actin (α-CA). At 24 h, this diminution was statistically significant; however, there was not a correlation with the highest level of DNA demethylation at the same period using Methylation-Sensitive High Resolution Melting-PCR (MS-HRM-PCR). An evident increase in the α-CA protein expression was observed by Western blotting in hATPCs treated with 5-aza at 24 h. The mRNA expression of α-SMA (α-smooth actin) also showed a time-dependent decrease after the treatment, however, it was not significant. The ultrastructural analysis showed similar structures such as like-cell junctions, caveolae, and actin myofilaments, which aligned in parallel. These phenotypic alterations were found only after the treatment; however, the hTAPCs after 5-aza treatment were not able to form thick myofilaments and consequently sarcomeres. These results indicated that a terminal cardiac differentiation of hTAPCs was not achieved and that the cardiomyogenesis failure could be related to the non-muscle origin of the adipose tissue.

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A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose Tissue

PLoS Genetics ◽

10.1371/journal.pgen.1003572 ◽

2013 ◽

Vol 9 (6) ◽

pp. e1003572 ◽

Cited By ~ 362

Author(s):

Tina Rönn ◽

Petr Volkov ◽

Cajsa Davegårdh ◽

Tasnim Dayeh ◽

Elin Hall ◽

...

Keyword(s):

Dna Methylation ◽

Adipose Tissue ◽

Exercise Intervention ◽

Human Adipose Tissue ◽

Methylation Pattern ◽

Genome Wide ◽

Dna Methylation Pattern

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DDR1 methylation is associated with bipolar disorder and the isoform expression and methylation of myelin genes

Epigenomics ◽

10.2217/epi-2021-0006 ◽

2021 ◽

Author(s):

Beatriz Garcia-Ruiz ◽

Manuel Castro de Moura ◽

Gerard Muntané ◽

Lourdes Martorell ◽

Elena Bosch ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Bipolar Disorder ◽

Mrna Expression ◽

Gene Expression Analysis ◽

Mrna Levels ◽

Healthy Controls ◽

Genome Wide ◽

Isoform Expression

Aim: To investigate DDR1 methylation in the brains of bipolar disorder (BD) patients and its association with DDR1 mRNA levels and comethylation with myelin genes. Materials & methods: Genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) corrected for glial composition and DDR1 gene expression analysis in the occipital cortices of individuals with BD (n = 15) and healthy controls (n = 15) were conducted. Results: DDR1 5-methylcytosine levels were increased and directly associated with DDR1b mRNA expression in the brains of BD patients. We also observed that DDR1 was comethylated with a group of myelin genes. Conclusion: DDR1 is hypermethylated in BD brain tissue and is associated with isoform expression. Additionally, DDR1 comethylation with myelin genes supports the role of this receptor in myelination.

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Bacterial Lipopolysaccharide Induced Alterations of Genome-Wide DNA Methylation and Promoter Methylation of Lactation-Related Genes in Bovine Mammary Epithelial Cells

Toxins ◽

10.3390/toxins11050298 ◽

2019 ◽

Vol 11 (5) ◽

pp. 298 ◽

Cited By ~ 9

Author(s):

Jingbo Chen ◽

Yongjiang Wu ◽

Yawang Sun ◽

Xianwen Dong ◽

Zili Wang ◽

...

Keyword(s):

Dna Methylation ◽

Immune Response ◽

Mrna Expression ◽

Promoter Methylation ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Bovine Mammary Epithelial Cells ◽

Genome Wide ◽

Immune Response Pathway ◽

Gene Mrna

Bacterial lipopolysaccharide (LPS) could result in poor lactation performance in dairy cows. High methylation of DNA is associated with gene repression. However, it is unclear whether LPS could suppress the expression of lactation-related genes by inducing DNA methylation. Therefore, the objective of this study was to investigate the impact of LPS on genome-wide DNA methylation, using methylated DNA immunoprecipitation with high-throughput sequencing (MeDIP-seq) and on the promoter methylation of lactation-related genes using MassArray analysis in bovine mammary epithelial cells. The bovine mammary epithelial cell line MAC-T cells were treated for 48 h with LPS at different doses of 0, 1, 10, 100, and 1000 endotoxin units (EU)/mL (1 EU = 0.1 ng). The results showed that the genomic methylation levels and the number of methylated genes in the genome as well as the promoter methylation levels of milk genes increased when the LPS dose was raised from 0 to 10 EU/mL, but decreased after further increasing the LPS dose. The milk gene mRNA expression levels of the 10 EU/mL LPS treatment were significantly lower than these of untreated cells. The results also showed that the number of hypermethylated genes was greater than that of hypomethylated genes in lipid and amino acid metabolic pathways following 1 and 10 EU/mL LPS treatments as compared with control. By contrast, in the immune response pathway the number of hypomethylated genes increased with increasing LPS doses. The results indicate LPS at lower doses induced hypermethylation of the genome and promoters of lactation-related genes, affecting milk gene mRNA expression. However, LPS at higher doses induced hypomethylation of genes involved in the immune response pathway probably in favor of immune responses.

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Genome-wide analysis of DNA methylation and their associations with long noncoding RNA/mRNA expression in non-small-cell lung cancer

Epigenomics ◽

10.2217/epi-2016-0120 ◽

2017 ◽

Vol 9 (2) ◽

pp. 137-153 ◽

Cited By ~ 13

Author(s):

Nannan Feng ◽

Yu Wang ◽

Min Zheng ◽

Xiao Yu ◽

Hongyan Lin ◽

...

Keyword(s):

Lung Cancer ◽

Dna Methylation ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Small Cell ◽

Small Cell Lung ◽

Genome Wide Analysis ◽

Genome Wide

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Neudesin Neurotrophic Factor Promotes Bovine Preadipocyte Differentiation and Inhibits Myoblast Myogenesis

Animals ◽

10.3390/ani9121109 ◽

2019 ◽

Vol 9 (12) ◽

pp. 1109 ◽

Cited By ~ 1

Author(s):

Xiaotong Su ◽

Yaning Wang ◽

Anqi Li ◽

Linsen Zan ◽

Hongbao Wang

Keyword(s):

Adipose Tissue ◽

Protein Expression ◽

Mrna Expression ◽

Neurotrophic Factor ◽

Muscle Development ◽

Expression Patterns ◽

Marker Genes ◽

Qinchuan Cattle ◽

Preadipocyte Differentiation ◽

Expression Levels

Neudesin neurotrophic factor (NENF) is a secreted protein that is essential in multiple biological processes, including neural functions, adipogenesis, and tumorigenesis. In our previous study, NENF was significantly inhibited in the bovine adipocytes-myoblasts co-culture system. However, studies on NENF regulation of bovine muscle development and involvement in the cross-talk between adipose tissue and skeletal muscle have not been reported. Hence, the aim of this study was to clarify the functional roles of NENF in bovine preadipocytes and myoblasts. Real-time quantitative PCR (RT-qPCR) was performed to examine the spatial expression patterns of NENF in different tissues, and the results showed that NENF was highly expressed in the muscle of four-day-old and 24-month-old Qinchuan cattle. Compared with four-day-old Qinchuan cattle, the expression level of NENF was significantly up-regulated in 24-month-old bovine adipose tissue. To explore the roles of NENF in bovine myoblast and preadipocyte differentiation, small interfering RNA (siRNA) targeting the NENF gene were transfected into bovine preadipocytes and myoblasts to knock down the expression of the NENF gene. The results showed that the knockdown of NENF in differentiating adipocytes attenuated lipid accumulation, decreased the mRNA expression of adipogenic key marker genes PPARγ, CEBPα, CEBPβ, FASN, and SCD1, and decreased the protein expression of PPARγ, CEBPα, and FASN. The formation of myotubes was significantly accelerated, and the mRNA expression levels of myogenic marker genes MYOD1, MYF5, MYF6, MEF2A, MEF2C, and CKM, and the protein expression levels of MYOD1, MYF6, MEF2A, and CKM were up-regulated in myoblasts where NENF was knocked down. In short, the knockdown of NENF inhibited preadipocyte differentiation and promoted myoblast myogenesis.

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An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss

Genome Biology ◽

10.1186/s13059-014-0569-x ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 136

Author(s):

Miles C Benton ◽

Alice Johnstone ◽

David Eccles ◽

Brennan Harmon ◽

Mark T Hayes ◽

...

Keyword(s):

Dna Methylation ◽

Weight Loss ◽

Gastric Bypass ◽

Adipose Tissue ◽

Human Adipose Tissue ◽

Before And After ◽

Obesity Genes

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The Impact of Exercise on DNA Methylation of Genes Associated with Type 2 Diabetes and Obesity in Human Adipose Tissue

US Endocrinology ◽

10.17925/use.2014.10.01.64 ◽

2014 ◽

Vol 10 (01) ◽

pp. 64 ◽

Cited By ~ 2

Author(s):

Tina Rönn ◽

Charlotte Ling ◽

◽

Keyword(s):

Type 2 Diabetes ◽

Dna Methylation ◽

Adipose Tissue ◽

Human Adipose Tissue ◽

Short Review ◽

Methylation Pattern ◽

Cellular Level ◽

Genetic And Environmental Factors ◽

The Impact

It is well established that exercise promotes health, and reduces people’s risks for developing type 2 diabetes and becoming obese. But just how exercise performs this, at a cellular level, and what molecular and physiologic steps are involved and in what order, are still not fully understood. Metabolic disorders are often influenced by interactions between genetic and environmental factors. One possible explanation for how the environment may influence the genome is through epigenetic mechanisms–that is–chemical modifications to the DNA itself. Epigenetic factors include, for example, DNA methylation, histone modifications, and different RNA-mediated processes, which all have the ability to bind to DNA or affect the chromatin structure and thereby change how specific genes are interpreted and expressed. In this short review, we focus on describing how exercise influences the genome-wide DNA methylation pattern, including candidate genes for obesity and type 2 diabetes, in human adipose tissue.

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