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. 2021 Mar 10:12:587440.
doi: 10.3389/fimmu.2021.587440. eCollection 2021.

Transcriptome and Differential Methylation Integration Analysis Identified Important Differential Methylation Annotation Genes and Functional Epigenetic Modules Related to Vitiligo

Yihuan Pu  1 , Xuenuo Chen  2 , Yangmei Chen  1 , Lingzhao Zhang  1 , Jiayi Chen  1 , Yujie Zhang  1 , Xinyi Shao  1 , Jin Chen  1
Affiliations

Transcriptome and Differential Methylation Integration Analysis Identified Important Differential Methylation Annotation Genes and Functional Epigenetic Modules Related to Vitiligo

Yihuan Pu et al. Front Immunol. .

Abstract

Vitiligo is an pigmentation disorder caused by a variety of pathogenic factors; its main pathophysiological conditions include oxidative stress, immune activation, and genetic background. Additionally, DNA methylation is often associated with the pathogenesis of vitiligo; however, the underlying mechanism remains unknown. In the present study, we used the Human Methylation 850K BeadChip platform to detect DNA methylation changes in the vitiligo melanocytes. We then integrated the results with the transcriptome data of vitiligo melanocytes and lesions to analyse the correlation between differentially methylated levels and differentially expressed genes. The results showed that there was a significant negative correlation between methylation levels and differentially expressed genes. Subsequently, we enriched GO and KEGG based on methylated differentially expressed genes (MDEGs) using R package ClusterProfiler, and the results were closely related to the pathogenesis of vitiligo. In addition, we also constructed a PPI network of MDEGs and excavated three important functional epigenetic modules, involving a total of 12 (BCL2L1, CDK1, ECT2, HELLS, HSP90AA1, KIF23, MC1R, MLANA, PBK, PTGS2, SOX10, and TYRP1) genes. These genes affect melanocyte melanogenesis, cellular oxidative stress and other important biological processes. Our comprehensive analysis results support the significant contribution of the status of DNA methylation modification to vitiligo, which will help us to better understand the molecular mechanism of vitiligo and explore new therapeutic strategies.

Keywords: 850K; MDEGs; PPI; functional epigenetic modules; vitiligo melanocyte.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of bioinformatics analysis. DMGs, Differentially methylated genes; DEGs, Differentially expressed genes; PIG1, human normal melanocyte; PIG3V, human vitiligo melanocyte.
Figure 2
Figure 2
(A) The heat map, (B) the Volcano map analysis of genes with differential methylation between vitiligo melanocyte and normal melanocyte. (C) A joint analysis of CNV results and differential methylation sites performde by the Circos diagram. CNV and the outermost circle represent chromosome regions, and the second inward circle represents the CNV copy number (red represents ratio > 0, green represents ratio < 0), The inner circle represents the DMR area.
Figure 3
Figure 3
Integrative analysis of methylome and transcriptome of vitiligo. (A) Veen diagram of differentially expressed genes between vitiligo skin lesion microarray and vitiligo melanocyte microarray. (B) Venn diagram between differentially methylated genes and differentially expressed genes of vitiligo. Correlation analysis between differentially methylated genes and differentially expressed genes: (C) negative correlation analysis, (D) positive correlation analysis.
Figure 4
Figure 4
GO and KEGG enrichment analysis of methylated-differentially expressed genes related with vitiligo melanocyte. Top 10 GO terms in (A) GO enrichment analysis of Hyper-MDGEs, (B) GO enrichment analysis of Hypo-MDGEs. (C) KEGG pathway analysis of Hyper-MDGEs, (D) KEGG pathway analysis of Hypo-MDGEs. The horizontal axes shows -log10 transformed P-value and p < 0.05 is considered significant.
Figure 5
Figure 5
(A) Protein-protein interaction network of MDEGs, Disconnected nodes were hid in the network. (B) Hub genes for MDEGs ranked in cytoHubba, functional epigenetic modules of the protein-protein interaction network: (C) module1, (D) module2, (E) module3.
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