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转录组与差异甲基化整合分析鉴定出与白癜风相关的重要差异甲基化注释基因和功能性表观遗传模块。

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

作者信息

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

机构信息

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

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

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.

摘要

白癜风是一种由多种致病因素引起的色素沉着障碍;其主要病理生理状况包括氧化应激、免疫激活和遗传背景。此外,DNA甲基化常与白癜风的发病机制相关;然而,其潜在机制仍不清楚。在本研究中,我们使用人类甲基化850K芯片平台检测白癜风黑素细胞中的DNA甲基化变化。然后,我们将结果与白癜风黑素细胞和皮损的转录组数据整合,分析差异甲基化水平与差异表达基因之间的相关性。结果表明,甲基化水平与差异表达基因之间存在显著负相关。随后,我们使用R包ClusterProfiler基于甲基化差异表达基因(MDEGs)进行GO和KEGG富集,结果与白癜风的发病机制密切相关。此外,我们还构建了MDEGs的蛋白质-蛋白质相互作用(PPI)网络,并挖掘出三个重要的功能性表观遗传模块,共涉及12个基因(BCL2L1、CDK1、ECT2、HELLS、HSP90AA1、KIF23、MC1R、MLANA、PBK、PTGS2、SOX10和TYRP1)。这些基因影响黑素细胞黑素生成、细胞氧化应激等重要生物学过程。我们的综合分析结果支持DNA甲基化修饰状态对白癜风有显著贡献,这将有助于我们更好地理解白癜风的分子机制并探索新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c809/8006451/2745c48b0e1b/fimmu-12-587440-g0001.jpg

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