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Characterization of chromatin accessibility in psoriasis

《医学前沿（英文）》 2022年第16卷第3期页码 483-495 doi: 10.1007/s11684-021-0872-3

摘要： The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.

关键词： psoriasis ATAC-seq epigenetics transcription factor

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DNA methylation-based subclassification of psoriasis in the Chinese Han population

Fusheng Zhou, Changbing Shen, Yi-Hsiang Hsu, Jing Gao, Jinfa Dou, Randy Ko, Xiaodong Zheng, Liangdan Sun, Yong Cui, Xuejun Zhang

《医学前沿（英文）》 2018年第12卷第6期页码 717-725 doi: 10.1007/s11684-017-0588-6

摘要： Psoriasis (Ps) is an inflammatory skin disease caused by genetic and environmental factors. Previous studies on DNA methylation (DNAm) found genetic markers that are closely associated with Ps, and evidence has shown that DNAm mediates genetic risk in Ps. In this study, Consensus Clustering was used to analyze DNAm data, and 114 Ps patients were divided into three subclassifications. Investigation of the clinical characteristics and copy number variations (CNVs) of , , and in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI) score. The proportion of late-onset (≥40 years) Ps patients was significantly higher in type I than in types II and III ( = 0.035). Type III contained the smallest proportion of smokers and the largest proportion of non-smoking Ps patients ( = 0.086). The CNVs of and showed no significant differences but the CNV of significantly differed among the three subclassifications ( = 0.044). This study is the first to profile Ps subclassifications based on DNAm data in the Chinese Han population. These results are useful in the treatment and management of Ps from the molecular and genetic perspectives.

关键词： psoriasis DNA methylation subclassification