First Author | Hildesheim J | Year | 1999 |
Journal | J Biol Chem | Volume | 274 |
Issue | 37 | Pages | 26399-406 |
PubMed ID | 10473598 | Mgi Jnum | J:57591 |
Mgi Id | MGI:1344985 | Doi | 10.1074/jbc.274.37.26399 |
Citation | Hildesheim J, et al. (1999) Characterization of the regulatory domains of the human skn-1a/Epoc-1/Oct-11 POU transcription factor. J Biol Chem 274(37):26399-406 |
abstractText | The Skn-1a POU transcription factor is primarily expressed in keratinocytes of murine embryonic and adult epidermis. Although some POU factors expressed in a tissue-specific manner are important for normal differentiation, the biological function of Skn-1a remains unknown. Previous in vitro studies indicate that Skn-1a has the ability to transactivate markers of keratinocyte differentiation. In this study, we have characterized Skn-1a's transactivation domain(s) and engineered a dominant negative protein that lacked this transactivation domain. Deletional analysis of the human homologue of Skn-1a with three target promoters revealed the presence of two functional domains: a primary C-terminal transactivation domain and a combined N-terminal inhibitory domain and transactivation domain. Skn-1a lacking the C-terminal region completely lost transactivation ability, irrespective of the promoter tested, and was able to block transactivation by normal Skn-1a in competition assays. Compared with full-length, Skn-1a lacking the N-terminal region demonstrated either increased transactivation (bovine cytokeratin 6 promoter), comparable transactivation (human papillomavirus type 1a long control region), or loss of transactivation (human papillomavirus type 18 long control 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-specific gene regulator. |