EGR3 is a late epidermal differentiation regulator that establishes the skin-specific gene network

Late epidermal differentiation is a key step of skin barrier formation; however, the specific genetic factors that distinguish late differentiation from early differentiation remain unknown. Here, we demonstrated that early growth response factor 3 (EGR3) is highly expressed in the stratum granulosum, and that it contributes to late epidermal differentiation. However, its expression is lost under poorly differentiated conditions such as the parakeratosis-lesional skin. EGR3 mediated the regulation of genes located in the epidermal differentiation complex (EDC) through activation of enhancers and induction of enhancer RNAs.