Epigenetic and Transcriptional Regulatory Networks Underlying Psoriasis Pathogenesis.

Psoriasis is a chronic, immune-mediated dermatological disorder characterized by hyperproliferation of keratinocytes and dysregulated immune signaling. Although genome-wide association studies (GWAS) have identified susceptibility loci, the disease's multifactorial nature underscores the importance of non-genetic regulatory mechanisms. Among these epigenetic modifications are those that critically link genetic predisposition with environmental stimuli. This review offers an in-depth overview of current insights into the role of epigenetic regulation in psoriasis' pathophysiology. Key mechanisms, including aberrant DNA methylation, histone post-translational modifications (e.g., H3K27ac, H3K4me3), and dysregulated non-coding RNAs (ncRNA), are discussed in the context of inflammatory signaling and immune cell function. This study explored how environmental factors such as ultraviolet radiation and air pollution induce epigenetic reprogramming that perpetuates pro-inflammatory states. Furthermore, it highlights the translational potential of targeting epigenetic regulators and epigenome editing technologies, including Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) fusion systems, as precision therapeutic strategies. In parallel, advances in single-cell epigenomics, spatial transcriptomics, and the profiling of circulating biomarkers offer novel diagnostic tools. Despite advances, challenges persist, including the limited predictive value of preclinical models and variable epigenetic profiles. Positioning epigenetics as the bridge between genetic risk, environmental triggers, and therapeutic advances, this review presents a precision medicine framework for psoriasis.