Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis
Dóra Romhányi1, Ágnes Bessenyei1, Kornélia Szabó1,2,3
1Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary.
International Journal of Molecular Sciences
|July 12, 2025
Summary
Histone methyltransferases show altered expression in psoriasis, impacting gene silencing, keratinocyte proliferation, and immune responses. These epigenetic changes are key to understanding psoriasis development.
Area of Science:
- Epigenetics
- Dermatology
- Molecular Biology
Background:
- Psoriasis pathogenesis involves complex epigenetic alterations.
- Limited studies exist on histone methyltransferases' role in psoriasis progression.
Purpose of the Study:
- To comprehensively analyze the differential expression of histone methyltransferases, particularly SET domain family members, in psoriasis.
- To investigate the role of aberrant histone methylation in psoriasis development.
Main Methods:
- Analysis of nearly 300 transcriptomes.
- Focus on differential expression of protein isoform-coding transcripts.
- Examination of SET domain family histone methyltransferases, including EZH2, ASH1L, NSD1, NSD2, SETD2, SUV39 family, PRDM family, and SETD8.
Main Results:
- EZH2 transcripts increased in lesional skin, suggesting altered H3K27 methylation and gene silencing.
- ASH1L showed reversed expression; NSD1/NSD2 upregulated; SETD2 downregulated in lesions, indicating disrupted H3K36 methylation.
- Altered expression observed in H3K9 methyltransferases (SUV39H2, EHMT1, SETDB2), PRDM family members, and H4K20 methyltransferases (SUV420H1, SETD8).
Conclusions:
- Aberrant expression and isoform variability of histone methyltransferases contribute to psoriasis pathogenesis.
- Dysregulation of keratinocyte proliferation, differentiation, and immune responses are linked to these epigenetic changes.
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