Assay for Transposase-Accessible Chromatin Using Sequencing Analysis Reveals a Widespread Increase in Chromatin Accessibility in Psoriasis

Psoriasis is a complex, chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and a 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 using an assay for transposase-accessible chromatin using sequencing analysis of 15 psoriatic, 9 nonpsoriatic, and 19 normal skin tissue samples, 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 an increased accessibility in psoriatic skin tissue. These differentially accessible regions tended to be more hypomethylated and correlated with the expression of their linked genes, which comprised several psoriasis susceptibility loci. Analyses of the differentially accessible region sequences showed that they were most highly enriched with FRA1 and/or activator protein-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 and/or activator protein-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. Psoriasis is a complex, chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and a 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 using an assay for transposase-accessible chromatin using sequencing analysis of 15 psoriatic, 9 nonpsoriatic, and 19 normal skin tissue samples, 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 an increased accessibility in psoriatic skin tissue. These differentially accessible regions tended to be more hypomethylated and correlated with the expression of their linked genes, which comprised several psoriasis susceptibility loci. Analyses of the differentially accessible region sequences showed that they were most highly enriched with FRA1 and/or activator protein-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 and/or activator protein-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.