Abstract

Psoriasis is a complex chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and disordered immune response; however, its exact etiology remains unknown. To better understand the regulatory network underlying psoriasis, we explored the landscape of chromatin accessibility by assay for transposase-accessible chromatin using sequencing (ATAC-seq) on 15 psoriatic, 9 nonpsoriatic, and 19 normal skin tissues, and the chromatin accessibility data were integrated with genomic, epigenomic, and transcriptomic datasets. We identified 4,915 genomic regions that displayed differential accessibility in psoriatic samples compared with both nonpsoriatic and normal samples, nearly all of which exhibited increased accessibility in psoriatic skin tissue. These differentially accessible regions (DARs) tended to be more hypomethylated and correlated with the expression of their linked genes, which comprised several psoriasis susceptibility loci. Analyses of the DAR sequences showed that they were most highly enriched for FRA1/AP-1 transcription factor DNA-binding motifs. We also found that AIM2, which encodes an important inflammasome component that triggers skin inflammation, is a direct target of FRA1/AP-1. Our study provided clear insights and resources for an improved understanding of the pathogenesis of psoriasis. These disease-associated accessible regions might serve as therapeutic targets for psoriasis treatment in the future.

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