Romhányi Dóra, Bessenyei Ágnes, Szabó Kornélia, Kemény Lajos, Gyulai Rolland, Groma Gergely
Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary.
Hungarian Centre of Excellence for Molecular Medicine-University of Szeged Skin Research Group (HCEMM-USZ Skin Research Group), H-6720 Szeged, Hungary.
Int J Mol Sci. 2025 Jun 30;26(13):6329. doi: 10.3390/ijms26136329.
Psoriasis involves complex epigenetic alterations, but detailed studies on histone methyltransferases and their role in disease progression are limited. We conducted a comprehensive analysis of nearly 300 transcriptomes, focusing mainly on differential expression of protein isoform-coding transcripts within the SET domain family of histone methyltransferases. Consistent with previous findings, EZH2 transcripts showed increased expression in lesional skin, indicating altered H3K27 methylation that may enhance gene silencing, promoting keratinocyte proliferation and inflammatory responses. In the SET2 family, ASH1L exhibited reversed expression patterns between non-lesional and lesional skin, while NSD1 and NSD2 were upregulated, and SETD2 downregulated in lesions, suggesting disrupted H3K36 methylation that may affect immune responses and keratinocyte proliferation. Among H3K9 methyltransferases, SUV39 members, SUV39H2 was upregulated in lesions, whereas EHMT1 transcripts increased in non-lesional skin, and SETDB2 decreased in lesions. Additionally, PRDM family members such as PRDM2, MECOM (PRDM3), PRDM6, and PRDM8 showed altered expression in lesional skin. The H4K20 methylating SUV4-20 subfamily member, a SUV420H1 transcript, and SETD8 belonging to the other SET domain-containing family of methyltransferases were significantly increased in non-lesional skin and in lesions, respectively. Overall, aberrant expression and isoform variability of histone methyltransferases likely contribute to psoriasis pathogenesis by dysregulating proliferation, differentiation, and immune responses.
银屑病涉及复杂的表观遗传改变，但关于组蛋白甲基转移酶及其在疾病进展中作用的详细研究有限。我们对近300个转录组进行了全面分析，主要关注组蛋白甲基转移酶SET结构域家族内蛋白质异构体编码转录本的差异表达。与先前的研究结果一致，EZH2转录本在皮损中表达增加，表明H3K27甲基化改变，这可能增强基因沉默，促进角质形成细胞增殖和炎症反应。在SET2家族中，ASH1L在非皮损和皮损皮肤之间表现出相反的表达模式，而NSD1和NSD2在皮损中上调，SETD2在皮损中下调，提示H3K36甲基化破坏，这可能影响免疫反应和角质形成细胞增殖。在H3K9甲基转移酶中，SUV39成员中，SUV39H2在皮损中上调，而EHMT1转录本在非皮损皮肤中增加，SETDB2在皮损中减少。此外，PRDM家族成员如PRDM2、MECOM（PRDM3）、PRDM6和PRDM8在皮损皮肤中表达改变。H4K20甲基化的SUV4 - 20亚家族成员、一个SUV420H1转录本以及属于另一个含SET结构域甲基转移酶家族的SETD8分别在非皮损皮肤和皮损中显著增加。总体而言，组蛋白甲基转移酶的异常表达和异构体变异性可能通过失调增殖、分化和免疫反应而导致银屑病发病机制。
