Dataset Information

Epigenetic Changes in Asthma: Role of DNA CpG Methylation.

ABSTRACT: For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the 'missing' heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.

SUBMITTER: Bae DJ

PROVIDER: S-EPMC6953489 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Epigenetic Changes in Asthma: Role of DNA CpG Methylation.

Bae Da Jeong DJ Jun Ji Ae JA Chang Hun Soo HS Park Jong Sook JS Park Choon Sik CS

Tuberculosis and respiratory diseases 20200101 1

For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the 'missing' heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the enviro ...[more]

PMID: 31905427

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Project description:BackgroundDNA shape analysis has demonstrated the potential to reveal structure-based mechanisms of protein-DNA binding. However, information about the influence of chemical modification of DNA is limited. Cytosine methylation, the most frequent modification, represents the addition of a methyl group at the major groove edge of the cytosine base. In mammalian genomes, cytosine methylation most frequently occurs at CpG dinucleotides. In addition to changing the chemical signature of C/G base pairs, cytosine methylation can affect DNA structure. Since the original discovery of DNA methylation, major efforts have been made to understand its effect from a sequence perspective. Compared to unmethylated DNA, however, little structural information is available for methylated DNA, due to the limited number of experimentally determined structures. To achieve a better mechanistic understanding of the effect of CpG methylation on local DNA structure, we developed a high-throughput method, methyl-DNAshape, for predicting the effect of cytosine methylation on DNA shape.ResultsUsing our new method, we found that CpG methylation significantly altered local DNA shape. Four DNA shape features-helix twist, minor groove width, propeller twist, and roll-were considered in this analysis. Distinct distributions of effect size were observed for different features. Roll and propeller twist were the DNA shape features most strongly affected by CpG methylation with an effect size depending on the local sequence context. Methylation-induced changes in DNA shape were predictive of the measured rate of cleavage by DNase I and suggest a possible mechanism for some of the methylation sensitivities that were recently observed for human Pbx-Hox complexes.ConclusionsCpG methylation is an important epigenetic mark in the mammalian genome. Understanding its role in protein-DNA recognition can further our knowledge of gene regulation. Our high-throughput methyl-DNAshape method can be used to predict the effect of cytosine methylation on DNA shape and its subsequent influence on protein-DNA interactions. This approach overcomes the limited availability of experimental DNA structures that contain 5-methylcytosine.

Dataset Information

Epigenetic Changes in Asthma: Role of DNA CpG Methylation.

Publications

Epigenetic Changes in Asthma: Role of DNA CpG Methylation.

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