Low Oxygen Consumption is Related to a Hypomethylation and an Increased Secretion of IL-6 in Obese Subjects with Sleep Apnea-Hypopnea Syndrome

Background: Deoxyribonucleic acid (DNA) methylation is an epigenetic modification involved in gene expression regulation, usually via gene silencing, which contributes to the risks of many multifactorial diseases. The aim of the present study was to analyze the influence of resting oxygen consumption on global and gene DNA methylation as well as protein secretion of inflammatory markers in blood cells from obese subjects with sleep apnea-hypopnea syndrome (SAHS). Methods: A total of 44 obese participants with SAHS were categorized in 2 groups according to their resting oxygen consumption. DNA methylation levels were evaluated using a methylation-sensitive high resolution melting approach. Results: The analyzed interleukin 6 (IL6) gene cytosine phosphate guanine (CpG) islands showed a hypomethylation, while serum IL-6 was higher in the low compared to the high oxygen consumption group (p < 0.05). Moreover, an age-related loss of DNA methylation of tumor necrosis factor (B = -0.82, 95% CI -1.33 to -0.30) and long interspersed nucleotide element 1 (B = -0.46; 95% CI -0.87 to -0.04) gene CpGs were found. Finally, studied CpG methylation levels of serpin peptidase inhibitor, clade E member 1 (r = 0.43; p = 0.01), and IL6 (r = 0.41; p = 0.02) were positively associated with fat-free mass. Conclusions: These findings suggest a potential role of oxygen in the regulation of inflammatory genes. Oxygen consumption measurement at rest could be proposed as a clinical biomarker of metabolic health.

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To Determine Pivotal Genes Driven by Methylated DNA in Obstructive Sleep Apnea Hypopnea Syndrome

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/5520325 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Yan Li ◽

Yajuan Zhang

Keyword(s):

Dna Methylation ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Molecular Mechanisms ◽

Sleep Apnea Syndrome ◽

Respiratory Dysfunction ◽

Obstructive Sleep ◽

Hypopnea Syndrome ◽

First Time ◽

Erbb2 Signaling

Obstructive sleep apnea syndrome (OSAHS) is a widespread respiratory dysfunction that has attracted more and more attention in recent years. Recently, a large number of studies have shown that abnormal DNA methylation epigenetically silences genes necessary for the pathogenesis of human diseases. However, the exact mechanism of abnormal DNA methylation in OSAHS is still elusive. In this study, we downloaded the OSAHS data from the GEO database. Our data for the first time revealed 520 hypermethylated genes and 889 hypomethylated genes in OSAHS. Bioinformatics analysis revealed that these abnormal methylated genes exhibited an association with the regulation of angiogenesis, apoptosis, Wnt, and ERBB2 signaling pathways. PPI network analysis displayed the interactions among these genes and validated several hub genes, such as GPSM2, CCR8, TAS2R20, TAS2R4, and TAS2R5, which were related to regulating liganded Gi-activating GPCR and the transition of mitotic metaphase/anaphase. In conclusion, our study offers a new hint of understanding the molecular mechanisms in OSAHS progression and will provide OSAHS with newly generated innovative biomarkers.

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Individual DNA Methylation Profile is Correlated with Age and can be Targeted to Modulate Healthy Aging and Longevity

Current Pharmaceutical Design ◽

10.2174/1381612825666191112095655 ◽

2019 ◽

Vol 25 (39) ◽

pp. 4139-4149 ◽

Cited By ~ 3

Author(s):

Francesco Guarasci ◽

Patrizia D'Aquila ◽

Alberto Montesanto ◽

Andrea Corsonello ◽

Dina Bellizzi ◽

...

Keyword(s):

Dna Methylation ◽

Mitochondrial Dna ◽

Aging Process ◽

Healthy Aging ◽

Nuclear Dna ◽

Epigenetic Modification ◽

Biological Aging ◽

Biomarkers Of Aging ◽

Age Related

: Patterns of DNA methylation, the best characterized epigenetic modification, are modulated by aging. In humans, different studies at both site-specific and genome-wide levels have reported that modifications of DNA methylation are associated with the chronological aging process but also with the quality of aging (or biological aging), providing new perspectives for establishing powerful biomarkers of aging. : In this article, the role of DNA methylation in aging and longevity has been reviewed by analysing literature data about DNA methylation variations occurring during the lifetime in response to environmental factors and genetic background, and their association with the aging process and, in particular, with the quality of aging. Special attention has been devoted to the relationship between nuclear DNA methylation patterns, mitochondrial DNA epigenetic modifications, and longevity. Mitochondrial DNA has recently been reported to modulate global DNA methylation levels of the nuclear genome during the lifetime, and, in spite of the previous belief, it has been found to be the target of methylation modifications. : Analysis of DNA methylation profiles across lifetime shows that a remodeling of the methylome occurs with age and/or with age-related decline. Thus, it can be an excellent biomarker of aging and of the individual decline and frailty status. The knowledge about the mechanisms underlying these modifications is crucial since it might allow the opportunity for targeted treatment to modulate the rate of aging and longevity.

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Heterozygous loss of ZBTB38 leads to early embryonic lethality in mice via suppressing Nanog and Sox2

10.1101/2021.08.19.456970 ◽

2021 ◽

Author(s):

Eishou Matsuda ◽

Miki Nishio ◽

Takuya Matsuura ◽

Shunya Hibi ◽

Shiomi Ohta ◽

...

Keyword(s):

Dna Methylation ◽

Cell Proliferation ◽

Gene Expression Regulation ◽

Epigenetic Modification ◽

Embryonic Lethality ◽

Biological Processes ◽

Es Cell ◽

Nanog Expression ◽

Early Embryonic Lethality ◽

Single Allele

Mammalian DNA methylation is an epigenetic modification which is involved in various biological processes, including gene expression regulation. In mice, methyltransferases are responsible for DNA methylation, which are critical for early embryogenesis. However, the significance of methyl-CpG binding proteins (MBPs) that bind methylated CpG remains largely unknown. We previously demonstrated that ZBTB38/CIBZ-a zinc finger type of MBP-is required for ES cell proliferation by positively regulating Nanog expression. However, the physiological function of ZBTB38 remains unclear. In this study, we generated conditional ZBTB38 knockout mice using Cre-loxP technology. Unexpectedly, our results showed that germline loss of the ZBTB38 single allele resulted in decreased epiblast cell proliferation and increased apoptosis shortly after implantation, leading to early embryonic lethality. We found that heterozygous loss of ZBTB38 reduced the expression of Nanog, Sox2, and the genes responsible for epiblast proliferation, differentiation, and cell viability. Despite this lethal phenotype, ZBTB38 is dispensable for ES cell establishment and identity. Together, these findings indicate that ZBTB38 is essential for early embryonic development, providing new insights into the roles of MBP in implantation.

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Epigenetic regulations through DNA methylation and hydroxymethylation: clues for early pregnancy in decidualization

BioMolecular Concepts ◽

10.1515/bmc-2013-0036 ◽

2014 ◽

Vol 5 (2) ◽

pp. 95-107 ◽

Cited By ~ 8

Author(s):

Fei Gao ◽

Sanjoy K. Das

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Cell Fate ◽

High Throughput Sequencing ◽

Gene Expression Regulation ◽

Epigenetic Modification ◽

Regulation Of Gene Expression ◽

Reproductive Organ ◽

Epigenetic Changes ◽

Dynamic Regulation

AbstractDNA methylation at cytosines is an important epigenetic modification that participates in gene expression regulation without changing the original DNA sequence. With the rapid progress of high-throughput sequencing techniques, whole-genome distribution of methylated cytosines and their regulatory mechanism have been revealed gradually. This has allowed the uncovering of the critical roles played by DNA methylation in the maintenance of cell pluripotency, determination of cell fate during development, and in diverse diseases. Recently, rediscovery of 5-hydroxymethylcytosine, and other types of modification on DNA, have uncovered more dynamic aspects of cell methylome regulation. The interaction of DNA methylation and other epigenetic changes remodel the chromatin structure and determine the state of gene transcription, not only permanently, but also transiently under certain stimuli. The uterus is a reproductive organ that experiences dramatic hormone stimulated changes during the estrous cycle and pregnancy, and thus provides us with a unique model for studying the dynamic regulation of epigenetic modifications. In this article, we review the current findings on the roles of genomic DNA methylation and hydroxymethylation in the regulation of gene expression, and discuss the progress of studies for these epigenetic changes in the uterus during implantation and decidualization.

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DNA Methylation in Neurodegenerative and Cerebrovascular Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms21062220 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2220 ◽

Cited By ~ 4

Author(s):

Olaia Martínez-Iglesias ◽

Iván Carrera ◽

Juan Carlos Carril ◽

Lucía Fernández-Novoa ◽

Natalia Cacabelos ◽

...

Keyword(s):

Dna Methylation ◽

Gene Expression Regulation ◽

Methylation Status ◽

Cerebrovascular Disorders ◽

Cerebrovascular Diseases ◽

Epigenetic Mechanism ◽

Mrna Levels ◽

Serum Samples ◽

Global Methylation ◽

Age Related

DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is to compare methylation status of healthy subjects with that of patients with Alzheimer’s, Parkinson’s or Cerebrovascular diseases. We also analyze methylation status of a transgenic Alzheimer’s disease mouse model (3xTg-AD). Our results show that both global methylation (n = 141) and hydroxymethylation (n = 131) levels are reduced in DNA samples from buffy coats of patients with neurodegenerative disorders and age-related cerebrovascular disease. The importance of methylation and hydroxymethylation reduction is stressed by the finding that DNMT3a mRNA levels are also downregulated in buffy coats of patients with Dementia (n = 25). Global methylation is also reduced in brain, liver and serum samples of 3xTg-AD vs. wild type mice, such as DNMT3a mRNA levels that are also decreased in the brain of 3xTg-AD (n = 10). These results suggest that the use of global methylation and hydroxymethylation levels, together with the study of DNMT3a expression, could be useful as a new diagnostic biomarker for these prevalent disorders.

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Regular, Intense Exercise Training as a Healthy Aging Lifestyle Strategy: Preventing DNA Damage, Telomere Shortening and Adverse DNA Methylation Changes Over a Lifetime

Frontiers in Genetics ◽

10.3389/fgene.2021.652497 ◽

2021 ◽

Vol 12 ◽

Author(s):

Maha Sellami ◽

Nicola Bragazzi ◽

Mohammad Shoaib Prince ◽

Joshua Denham ◽

Mohamed Elrayess

Keyword(s):

Dna Methylation ◽

Dna Damage ◽

Exercise Training ◽

Epigenetic Modification ◽

Methylation Status ◽

The Body ◽

Training Load ◽

Activity Level ◽

Biological Aging ◽

Age Related

Exercise training is one of the few therapeutic interventions that improves health span by delaying the onset of age-related diseases and preventing early death. The length of telomeres, the 5′-TTAGGGn-3′ tandem repeats at the ends of mammalian chromosomes, is one of the main indicators of biological age. Telomeres undergo shortening with each cellular division. This subsequently leads to alterations in the expression of several genes that encode vital proteins with critical functions in many tissues throughout the body, and ultimately impacts cardiovascular, immune and muscle physiology. The sub-telomeric DNA is comprised of heavily methylated, heterochromatin. Methylation and histone acetylation are two of the most well-studied examples of the epigenetic modifications that occur on histone proteins. DNA methylation is the type of epigenetic modification that alters gene expression without modifying gene sequence. Although diet, genetic predisposition and a healthy lifestyle seem to alter DNA methylation and telomere length (TL), recent evidence suggests that training status or physical fitness are some of the major factors that control DNA structural modifications. In fact, TL is positively associated with cardiorespiratory fitness, physical activity level (sedentary, active, moderately trained, or elite) and training intensity, but is shorter in over-trained athletes. Similarly, somatic cells are vulnerable to exercise-induced epigenetic modification, including DNA methylation. Exercise-training load, however, depends on intensity and volume (duration and frequency). Training load-dependent responses in genomic profiles could underpin the discordant physiological and physical responses to exercise. In the current review, we will discuss the role of various forms of exercise training in the regulation of DNA damage, TL and DNA methylation status in humans, to provide an update on the influence exercise training has on biological aging.

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Early life DNA methylation profiles are indicative of age-related transcriptome changes

10.1101/557892 ◽

2019 ◽

Author(s):

Niran Hadad ◽

Dustin R. Masser ◽

Laura Blanco-Berdugo ◽

David R. Stanford ◽

Willard M. Freeman

Keyword(s):

Dna Methylation ◽

Early Life ◽

Functional Outcomes ◽

Brain Aging ◽

Epigenetic Modification ◽

Integrated Analysis ◽

Epigenetic Variability ◽

Age Related ◽

Developmental Origins Of Disease ◽

Methylation Patterns

AbstractAlterations to cellular and molecular programs with brain aging result in cognitive impairment and susceptibility to neurodegenerative disease. Changes in DNA methylation patterns, an epigenetic modification required for various CNS functions, are observed with aging and can be prevented by anti-aging interventions, but the functional outcomes of altered methylation on transcriptome profiles are poorly understood with brain aging. Integrated analysis of the hippocampal methylome and transcriptome with aging of male and female mice demonstrates that age-related differences in methylation and gene expression are anti-correlated within gene bodies and enhancers, but not promoters. Methylation levels at young age of genes altered with aging are positively associated with age-related expression changes even in the absence of significant changes to methylation with aging, a finding also observed in mouse Alzheimer’s models. DNA methylation patterns established in youth, in combination with other epigenetic marks, are able to predict changes in transcript trajectories with aging. These findings are consistent with the developmental origins of disease hypothesis and indicate that epigenetic variability in early life may explain differences in age-related disease.

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Early-life DNA methylation profiles are indicative of age-related transcriptome changes

Epigenetics & Chromatin ◽

10.1186/s13072-019-0306-5 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 5

Author(s):

Niran Hadad ◽

Dustin R. Masser ◽

Laura Blanco-Berdugo ◽

David R. Stanford ◽

Willard M. Freeman

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Early Life ◽

Brain Aging ◽

Epigenetic Modification ◽

Age Related ◽

Developmental Origins Of Disease ◽

Altered Gene ◽

Methylation Patterns ◽

Relationship Of

Abstract Background Alterations to cellular and molecular programs with brain aging result in cognitive impairment and susceptibility to neurodegenerative disease. Changes in DNA methylation patterns, an epigenetic modification required for various CNS functions are observed with brain aging and can be prevented by anti-aging interventions, but the relationship of altered methylation to gene expression is poorly understood. Results Paired analysis of the hippocampal methylome and transcriptome with aging of male and female mice demonstrates that age-related differences in methylation and gene expression are anti-correlated within gene bodies and enhancers. Altered promoter methylation with aging was found to be generally un-related to altered gene expression. A more striking relationship was found between methylation levels at young age and differential gene expression with aging. Highly methylated gene bodies and promoters in early life were associated with age-related increases in gene expression even in the absence of significant methylation changes with aging. As well, low levels of methylation in early life were correlated to decreased expression with aging. This relationship was also observed in genes altered in two mouse Alzheimer’s models. Conclusion DNA methylation patterns established in youth, in combination with other epigenetic marks, were able to accurately predict changes in transcript trajectories with aging. These findings are consistent with the developmental origins of disease hypothesis and indicate that epigenetic variability in early life may explain differences in aging trajectories and age-related disease.

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Whole genome analysis of the methylome and hydroxymethylome in normal and malignant lung and liver

10.1101/062588 ◽

2016 ◽

Cited By ~ 1

Author(s):

Xin Li ◽

Yun Liu ◽

Tal Salz ◽

Kasper D. Hansen ◽

Andrew Feinberg

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Gene Expression Regulation ◽

Cpg Island ◽

Epigenetic Modification ◽

Dna Demethylation ◽

Regulatory Function ◽

Whole Genome ◽

Strong Positive Correlation ◽

Active Genes

AbstractDNA methylation at the 5-postion of cytosine (5mC) is a well-established epigenetic modification which regulates gene expression and cellular plasticity in development and disease. The ten-eleven translocation (TET) gene family is able to oxidize 5mC to 5-hydroxymethyl-cytosine (5hmC), providing an active mechanism for DNA demethylation, and may also provide its own regulatory function. Here we applied oxidative bisulfite sequencing to generate whole-genome DNA methylation and hydroxymethylation maps at single-base resolution in paired human liver and lung normal and cancer. We found that 5hmC is significantly enriched in CpG island (CGI) shores while depleted in CGIs themselves, in particular at active genes, resulting in a 5hmC but not 5mC bimodal distribution around CGI corresponding to H3K4me1 marks. Hydroxymethylation on promoters, gene bodies, and transcription termination regions showed strong positive correlation with gene expression within and across tissues, suggesting that 5hmC is a mark of active genes and could play a role gene expression mediated by DNA demethylation. Comparative analysis of methylomes and hydroxymethylomes revealed that 5hmC is significantly enriched in both tissue specific DMRs (t-DMRs) and cancer specific DMRs (c-DMRs), and 5hmC is negatively correlated with methylation changes, particularly in non-CGI associated DMRs. Together these findings indicate that changes in 5mC as well as in 5hmC and coupled to H3K4me1 correspond to differential gene expression in tissues and matching tumors, revealing an intricate gene expression regulation through interplay of methylome, hydroxyl-methylome, and histone modifications.

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