biostudies-literatureRomhanyi DThis research was funded by the National Research, Development and Innovation Office (NKFIH, OTKA K143576 research grant), and received funding from the EU's Horizon 2020 re-search and innovation program under grant agreement No. 739593. This project also6329https://www.ebi.ac.uk/biostudies/studies/S-EPMC12249604biostudies-literatureUnknown26(13)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 H3K36International journal of molecular sciencesUnveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis.PMC12249604NKFIH, OTKA K143576;Bessenyei AKemeny LSzabo KGroma GRomhanyi DGyulai RfalseUnveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis.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 H3K362025-01-01T00:00:00Z2025 Jun2026-07-02T03:19:42.706Z2026-07-02T03:12:16.334ZS-EPMC122496044065010810.3390/ijms26136329