FOSL1-associated condensates modulate superenhancer-mediated selected IL-1 family gene activation in psoriasis.

FOSL1-enriched superenhancers activate IL-1 family genes (IL1A, IL1B, IL36G) in psoriatic lesions, linked to condensate formation and EP300/H3K27 acetylation maintenance.

• Why it matters: Upstream epigenetic mechanisms that drive abnormal keratinocyte gene expression in psoriasis are unclear, limiting targeted therapies.
• What they did: Multiomics (ChIP-seq, CUT&Tag, ATAC-seq, RNA-seq) plus CRISPR superenhancer editing, condensate assays, and 3C sequencing were used in psoriatic lesions, perilesional skin, healthy skin, and M5-stimulated HaCaT cells.
• The result: BET inhibition reduced superenhancer activity and IL-1 cytokines and relieved psoriasis-like inflammation in vivo, while macrophage-derived IL-1 up-regulated FOSL1 via MAPK/ERK, amplifying inflammation.