434 Molecular events in the epidermis upon aryl hydrocarbon receptor targeting: AHR-TFAP2A axis drives epidermal keratinocyte differentiation

The aryl hydrocarbon receptor (AHR) is an environmental sensor and ligand-activated transcription factor that involved in epithelial homeostasis barrier development of the skin. Through genome-wide transcriptomic epigenomic analyses human primary keratinocytes upon AHR activation using TCDD we identified early late responsive genes. genes were enriched for canonical factors known to promote keratinocyte differentiation, development, host defense, such as Transcription Factor AP-2α (TFAP2A). Genes related epidermal differentiation structure (e.g. filaggrin, keratins, transglutaminases), defense PI3 S100 genes) DNA binding motif analysis siRNA-based knockdown TFAP2A expression indicated regulates differentiation. CRISPR-Cas9 mediated knockout resulted severely impeded stratification, terminal additional functional formation 3D equivalent cultures. herein AHR-TFAP2A axis provides important insights into response cues, which opens new avenues targeting this treat dysfunction diseases.