Allergy Asthma Respir Dis.  2013 Mar;1(1):4-10. 10.4168/aard.2013.1.1.4.

Asthma and epigenetics

• Bae DJ
• Park CS

• KMID: 2263053
• DOI: http://doi.org/10.4168/aard.2013.1.1.4

Abstract

For the past two decades, a huge number of genetic studies have been conducted to identify the genetic variants responsible for asthma risk. Several types of genetic and genomic approaches, including linkage analysis, candidate gene single nucleotide polymorphism studies, and whole genome-wide association studies have been applied. However, the genetic impacts of these studies are minimal because asthma is a complex syndrome affected by interaction with many environmental factors mediated by epigenetics. Epigenetics is alteration of genetic expression without changes of DNA sequence. Three major forms of epigenetic is DNA methylation, histone modfications and specific microRNA expression that are known to have vast effects on gene expression. However, knowledge regarding the epigenetic effect on the development of asthma and its traits is limited up to date. Recently, new data on epigenetics have been brought up to explain the phenotypic alterations of asthma. In this review, we present general concept of epigenetics, environmental factors inducting epigenetic changes and the background mechanisms in epigenetics behind development asthma and epigenetic therapy.

Keyword

Asthma; Epigenetics; Gene; DNA methylation; Genome

MeSH Terms

Asthma
Base Sequence
DNA Methylation
Epigenomics
Gene Expression
Genetic Association Studies
Genome
Genome-Wide Association Study
Histones
MicroRNAs
Polymorphism, Single Nucleotide
Histones
MicroRNAs

Figure

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  Fig. 1. Three mechanisms of epigenetics. SAM, S-Adenosylmethionine; DNMT, DNA methyl transferase.

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  Fig. 2. DNA metylation, chromatin remodeling of the gene expression. (A) The DNA methylation machinery interacts with the histone modification machinery. (B) DN-MTs, MeCP2, HDAC3 and MBPs recognized by other transcriptional regulators. TF, transcription Factor; PolII, DNA polymerase II; HAT, histone acetyltransferase; MBP, methyl-bindg protein; MeCP2, methyl CpG binding protein; DNMT, DNA methyl transferase; HDAC, histone deacetylases.

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  Fig. 3. Nucleosome structure and histone acetylation of a lysine. (A) Histones H2A, H2B, H3 and H4 are known as the core histones, this nucleosome has six N-termi-nal tail domains and two C-terminal tails. (B) Histone acetyltransferases histone acetyltransferases and histone deacetylases histone deacetylases recognized by other transcriptional regulators. K, lysine; P, phosphate; Ub, ubiquitin; S, serine; E, glutamic acid; C, carboxyl terminus; N, amino terminus; H, histone.

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  Fig. 4. Odd ratio of single nucleotide mutations and genes associated with asthma and asthma phenotypes (2003–2010, Soonchunhyang Genome Research Center). Single base mutations of the genes involved in innate immune process-es and acquired immunity, of asthma-related risk. IL, interleukin; TLR, toll-like receptors; CD4, cluster of differentiation 4; FcRI, high-affinity immunoglobulin E receptor; NFAT, nuclear factor of activated T-cells; API, arrowhead proteinase in-hibitor; GATA, globin transcription factor; NFkB, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; CXCR, C-X-C chemokine receptor type; CTNNA, catenin; CSF1R, colony stimulating factor 1 receptor; PPAR, peroxisome proliferator-activated receptor; MCP3, chemokine (C-C motif) ligand; DCNP1, chromosome 5 open reading frame; RUX1, runt-related transcription factor 1; ITK, IL 2-inducible T-cell kinase; STAT, signal transducer and activator of transcription; ADAM, metallopeptidase domain; MYLK, myosin light chain kinase.

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  Fig. 5. Factors associated with the type of inflammatory cells to determine the diversity of the asthma phenotype. BaP, benzophenone; PAH, polycyclic aromatic hydrocarbons; DEP, diesel exhaust particles; PM, particulate matter; LPS, lipo-polysaccharide; IL, interleukin; TH cell, T helper cell; IFN, interferon; TGF-β, transforming growth factor beta; GATA, globin transcription factor; FOXP3, fork-head box P3; T-bet, T-box transcription factor.

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