The hSkn-1a POU transcription factor enhances epidermal stratification by promoting keratinocyte proliferation

Skn-1a is a POU transcription factor that is primarily expressed in the epi dermis and is known to modulate the expression of several genes associated with keratinocyte differentiation. However, the formation of a stratified e pidermis requires a carefully controlled balance between keratinocyte proli feration and differentiation, and a role for Skn-1a in this process has not been previously demonstrated. Here, our results show, surprisingly, that h uman Skn-1a contributes to epidermal stratification by primarily promoting keratinocyte proliferation and secondarily by enhancing the subsequent kera tinocyte differentiation. In organotypic raft cultures of both primary huma n keratinocytes and immortalized HaCaT keratinocytes, human Skn-1a expressi on is associated with increased keratinocyte proliferation and re-epithelia lization of the dermal substrates, resulting in increased numbers of kerati nocytes available for the differentiation process. in these same raft cultu res, human Skn-1a expression enhances the phenotypic changes or keratinocyt e differentiation and the upregulated expression of keratinocyte differenti ation genes. Conversely, expression of a dominant negative human Skn-1a tra nscription factor lacking the C-terminal transactivation domain blocks kera tinocytes from proliferating and stratifying, Keratinocyte stratification i s dependent on a precise balance between keratinocyte proliferation and dif ferentiation, and our results suggest that human Skn-1a has an important ro le in maintaining epidermal homeostasis by promoting keratinocyte prolifera tion.