Characterization of the regulatory domains of the human Skn-1a/Epoc-1/Oct-11 POU transcription factor

The Skn-1a POU transcription factor is primarily expressed in keratinocytes of murine embryonic and adult epidermis. Although some POU factors express ed in a tissue-specific manner are important for normal differentiation, th e biological function of Skn-1a remains unknown. Previous in vitro studies indicate that Skn-1a has the ability to transactivate markers of keratinocy te differentiation. In this study, we have characterized Skn-1a's transacti vation domain(s) and engineered a dominant negative protein that lacked thi s transactivation domain. Deletional analysis of the human homologue of Skn -1a with three target promoters revealed the presence of two functional dom ains: a primary C-terminal transactivation domain and a combined N-terminal inhibitory domain and transactivation domain. Skn-1a lacking the C-termina l region completely lost transactivation ability, irrespective of the promo ter tested, and was able to block transactivation by normal Skn-1a in compe tition assays. Compared with full-length, Skn-1a lacking the N-terminal reg ion demonstrated either increased transactivation (bovine cytokeratin 6 pro moter), comparable transactivation (human papillomavirus type 1a long contr ol region), or loss of transactivation (human papillomavirus type 18 long c ontrol region). The identification of a primary C-terminal transactivation domain enabled us to generate a dominant negative Skn-1a factor, which will be useful in the quest for a better understanding of this keratinocyte-spe cific gene regulator.