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Multiomics analyses identified epigenetic modulation of the S100A gene family in Kawasaki disease and their significant involvement in neutrophil transendothelial migration.

Abstract：

BACKGROUND:Kawasaki disease (KD) is a prevalent pediatric disease worldwide and can cause coronary artery aneurysm as a severe complication. Typically, DNA methylation is thought to repress the expression of nearby genes. However, the cases in which DNA methylation promotes gene expression have been reported. In addition, globally, to what extent DNA methylation affects gene expression and how it contributes to the pathogenesis of KD are not yet well understood. METHODS:To address these important biological questions, we enrolled subjects, collected DNA and RNA samples from the subjects' total white blood cells, and performed DNA methylation (M450K) and gene expression (HTA 2.0) microarray assays. RESULTS:By analyzing the variation ratios of CpG beta values (methylation percentage) and gene expression intensities, we first concluded that the CpG markers close (- 1500 bp to + 500 bp) to the transcription start sites had higher variation ratios, reflecting significant regulation capacities. Next, we observed that, globally speaking, gene expression was modestly negatively correlated (correlation rho ≈ - 0.2) with the DNA methylation status of both upstream and downstream CpG markers in the promoter region. Third, we found that specific CpG markers were hypo-methylated in disease samples compared with healthy samples and hyper-methylated in convalescent samples compared with disease samples, promoting and repressing S100A genes' expressions, respectively. Finally, using an in vitro cell model, we demonstrated that S100A family proteins enhanced leukocyte transendothelial migration in KD. CONCLUSIONS:This is the first study to integrate genome-wide DNA methylation with gene expression assays in KD and showed that the S100A family plays important roles in the pathogenesis of KD.

journal_name

Clin Epigenetics

journal_title

Clinical epigenetics

authors

Huang LH,Kuo HC,Pan CT,Lin YS,Huang YH,Li SC

doi

10.1186/s13148-018-0557-1

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

135

issue

eissn

1868-7075

issn

1868-7083

pii

10.1186/s13148-018-0557-1

journal_volume

pub_type

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Multiomics analyses identified epigenetic modulation of the S100A gene family in Kawasaki disease and their significant involvement in neutrophil transendothelial migration.