Identification of transcriptional regulators of psoriasis from RNA-Seq experiments

Abstract

Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the molecular mechanisms of regulation of the disease we performed RNA sequencing (RNA-Seq) analysis of 14 pairs of skin samples collected from psoriatic patients. Subsequent pathway analysis and an extraction of transcriptional regulators governing psoriasis-associated pathways was executed using a combination of MetaCore Interactome enrichment tool and cisExpress algorithm, and followed by comparison to a set of previously described psoriasis response elements. A comparative approach has allowed us to identify 42 core transcriptional regulators of the disease associated with inflammation (NFkB, IRF9, JUN, FOS, SRF), activity of T-cells in the psoriatic lesions (STAT6, FOXP3, NFATC2, GATA3, TCF7, RUNX1, etc.), hyperproliferation and migration of keratinocytes (JUN, FOS, NFIB, TFAP2A, TFAP2C), and lipid metabolism (TFAP2, RARA, VDR). After merging the ChIP-seq and RNA-seq data, we conclude that the atypical expression of FOXA1 transcriptional factor is an important player in psoriasis, as it inhibits maturation of naive T cells into this Treg subpopulation (CD4+FOXA1+CD47+CD69+PD-L1(hi)FOXP3−), therefore contributing to the development of psoriatic skin lesions.