Table_2_Genome-wide DNA methylation of Munro’s microabscess reveals the epigenetic regulation in the pathogenesis of psoriasis.xlsx

IntroductionMunro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.
MethodsPerformed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.
ResultsWe observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.
DiscussionIn conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.

**引言** 芒罗微脓肿（Munro's microabscess）是银屑病早期皮损的典型病理特征，主要表现为中性粒细胞在表皮内聚集。目前针对芒罗微脓肿的DNA甲基化（DNA methylation）微环境、其与转录的串扰以及其对中性粒细胞的调控作用尚未被阐明。
**方法** 本研究针对两批队列样本（发现队列含114例既往样本，验证队列含21例新收集样本）中伴或不伴芒罗微脓肿的银屑病皮损，开展全基因组DNA甲基化分析及进一步的差异甲基化分析。使用GO、MEME等工具对差异甲基化位点（differentially methylated sites, DMSs）进行下游功能分析，并对甲基化水平与转录组数据开展相关性分析。
**结果** 本研究共筛选得到647个与芒罗微脓肿相关的重叠差异甲基化位点。后续GO通路分析显示，DNA甲基化可能通过黏着斑（focal adhesion）及细胞-基质连接（cell-substrate junction）影响皮肤细胞的物理特性，并可能介导表皮内中性粒细胞的招募。通过MEME工具对647个差异甲基化位点周边20个基序的潜在结合转录因子（transcription factors, TFs）进行分析后发现，DNA甲基化可通过转化生长因子β（TGF-beta）通路及TH17通路，调控AP1家族成员的结合活性，并介导表皮内中性粒细胞的招募。同时结合本研究前期转录组数据，本研究发现DNA甲基化可调控CFDP、SIRT6、SMG6、TRAPPC9、HSD17B7及KIAA0415的表达，提示上述基因可能参与促进芒罗微脓肿的发生发展过程。
**讨论** 综上，DNA甲基化可通过调控银屑病皮损内芒罗微脓肿的进展，进而影响银屑病的病程。