Histone and Histone Acetylation-Related Alterations of Gene Expression in Uninvolved Psoriatic Skin and Their Effects on Cell Proliferation, Differentiation, and Immune Responses

Abstract

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.

Keywords: histone; histone acetylation and deacetylation; immune responses; proliferation; psoriasis; uninvolved skin.

Figure 1

Heatmap of histone and histone acetylation-related molecules with altered expression in uninvolved psoriatic skin (NL) and their expression in lesional skin (L) compared with healthy skin (H).

Figure 2

Replication-dependent and -independent histones with altered expression in psoriatic uninvolved skin and their effects on cell proliferation and immune system-related processes.

Figure 3

Altered expression of histone chaperones in uninvolved skin (depicted in blue) and their role in cell proliferation and immune system-related processes.

Figure 4

Effects on cell proliferation and immune system-related processes of histone acetyltransferase complex components with altered transcription in uninvolved skin (depicted in blue).

Figure 5

The impact of differentially expressed HDACs (A) and HDAC complexes (B) (depicted in blue) on proliferation, differentiation, and immune regulation in uninvolved skin.

Figure 5

The impact of differentially expressed HDACs (A) and HDAC complexes (B) (depicted in blue) on proliferation, differentiation, and immune regulation in uninvolved skin.