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. 2023 Sep 26;24(19):14551. doi: 10.3390/ijms241914551.
Psoriasis is a chronic immune-mediated skin disease in which the symptom-free, uninvolved skin carries alterations in gene expression, serving as a basis for lesion formation. Histones and histone acetylation-related processes are key regulators of gene expression, controlling cell proliferation and immune responses. Dysregulation of these processes is likely to play an important role in the pathogenesis of psoriasis. To gain a complete overview of these potential alterations, we performed a meta-analysis of a psoriatic uninvolved skin dataset containing differentially expressed transcripts from nearly 300 individuals and screened for histones and histone acetylation-related molecules. We identified altered expression of the replication-dependent histones HIST2H2AA3 and HIST2H4A and the replication-independent histones H2AFY, H2AFZ, and H3F3A/B. Eight histone chaperones were also identified. Among the histone acetyltransferases, ELP3 and KAT5 and members of the ATAC, NSL, and SAGA acetyltransferase complexes are affected in uninvolved skin. Histone deacetylation-related alterations were found to affect eight HDACs and members of the NCOR/SMRT, NURD, SIN3, and SHIP HDAC complexes. In this article, we discuss how histone and histone acetylation-related expression changes may affect proliferation and differentiation, as well as innate, macrophage-mediated, and T cell-mediated pro- and anti-inflammatory responses, which are known to play a central role in the development of psoriasis.
银屑病是一种慢性免疫介导的皮肤疾病，其中无症状、未受累的皮肤存在基因表达改变，这是病变形成的基础。组蛋白和组蛋白乙酰化相关过程是基因表达的关键调节剂，控制着细胞增殖和免疫反应。这些过程的失调可能在银屑病的发病机制中发挥重要作用。为了全面了解这些潜在的改变，我们对包含近 300 个人的银屑病未受累皮肤数据集进行了荟萃分析，并筛选了组蛋白和组蛋白乙酰化相关分子。我们发现复制依赖性组蛋白 HIST2H2AA3 和 HIST2H4A 以及复制非依赖性组蛋白 H2AFY、H2AFZ 和 H3F3A/B 的表达发生改变。还鉴定出了 8 种组蛋白伴侣。在组蛋白乙酰转移酶中，ELP3 和 KAT5 以及 ATAC、NSL 和 SAGA 乙酰转移酶复合物的成员在未受累皮肤中受到影响。组蛋白去乙酰化相关改变影响了 8 种 HDAC 和 NCOR/SMRT、NURD、SIN3 和 SHIP HDAC 复合物的成员。在本文中，我们讨论了组蛋白和组蛋白乙酰化相关表达变化如何影响增殖和分化，以及先天、巨噬细胞介导和 T 细胞介导的促炎和抗炎反应，这些反应已知在银屑病的发展中起核心作用。
