Lili Tang1, Yuyan Cheng1, Caihong Zhu1, Chao Yang1, Lu Liu1, Yuanjing Zhang1, Leilei Wen1, Xuejun Zhang2, Fusheng Zhou3, Sen Yang4. 1. Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, China; The Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, 230032, China. 2. Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, China; Institute of Dermatology and Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China; The Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, 230032, China. 3. Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, China; The Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, 230032, China. Electronic address: Biozhoufs@163.com. 4. Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, China; The Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, 230032, China. Electronic address: yang2004sen@163.com.
Abstract
BACKGROUND: Recent studies have revealed that DNA methylation (DNAm) could modulate gene expression in psoriasis (Ps). However, the relationship between whole-genome DNAm and gene expression in Ps has not been studied yet. OBJECTIVES: To better characterize the relationship between DNAm and gene expression, and to identify biological pathways triggered by changes in methylation involved in the pathogenesis of Ps. METHODS: Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were analysed by comparing 20 involved psoriatic (PP) skin, 20 uninvolved psoriatic (PN) skin and 20 normal (NN) skin biopsies. DEGs in negative correlation with the methylation were entered into further Gene Ontology (GO) and pathway analysis by clusterProfiler package in R program. RESULTS: A total of 290 genes with reverse correlation overlapped in PP vs PN and PP vs NN comparisons. GO categories of reversely-associated genes mainly enriched in T cell activation, type I interferon signaling pathway and defense response to other organism. Pathway analysis revealed superior NOD-like receptor signaling pathway and Measles enriched in the differentially up-regulated transcripts and regulation of lipolysis in adipocytes in the down-regulated transcripts. CONCLUSIONS: Our results provided a comprehensive correlation analysis of transcriptome and methylome in Ps. Increased innate immunity and decreased lipid biosynthesis play important roles in the development of psoriatic skin. This integrated analysis shed light on novel insights into the pathogenic mechanisms involved in Ps.
BACKGROUND: Recent studies have revealed that DNA methylation (DNAm) could modulate gene expression in psoriasis (Ps). However, the relationship between whole-genome DNAm and gene expression in Ps has not been studied yet. OBJECTIVES: To better characterize the relationship between DNAm and gene expression, and to identify biological pathways triggered by changes in methylation involved in the pathogenesis of Ps. METHODS: Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were analysed by comparing 20 involved psoriatic (PP) skin, 20 uninvolved psoriatic (PN) skin and 20 normal (NN) skin biopsies. DEGs in negative correlation with the methylation were entered into further Gene Ontology (GO) and pathway analysis by clusterProfiler package in R program. RESULTS: A total of 290 genes with reverse correlation overlapped in PP vs PN and PP vs NN comparisons. GO categories of reversely-associated genes mainly enriched in T cell activation, type I interferon signaling pathway and defense response to other organism. Pathway analysis revealed superior NOD-like receptor signaling pathway and Measles enriched in the differentially up-regulated transcripts and regulation of lipolysis in adipocytes in the down-regulated transcripts. CONCLUSIONS: Our results provided a comprehensive correlation analysis of transcriptome and methylome in Ps. Increased innate immunity and decreased lipid biosynthesis play important roles in the development of psoriatic skin. This integrated analysis shed light on novel insights into the pathogenic mechanisms involved in Ps.