THE EPIDERMIS - GENES ON - GENES OFF

The epidermal keratinocyte stem cell is distinguished by a relatively undifferentiated phenotype and an ability to proliferate. As part of a carefully orchestrated process, the offspring of these stem cells los e the ability to proliferate and begin a process of morphologic and bi ochemical transformation that results in their conversion into corneoc ytes. This process requires the coordinated expression of a host of ce llular genes. The mechanisms responsible for regulation of these genes is an area of intense interest. In keratinocytes, as in other cell ty pes, the expression of most genes is regulated at the transcriptional level by a class of proteins called transcription factors. Transcripti on factors are nuclear proteins that regulate transcription by mediati ng the final steps in the relay of information from the cell surface t o the nucleus and the gene. These factors bind to specific DNA sequenc e elements located within the target gene. In this brief review we sum marize evidence implicating activator protein 1 (AP1), AP2, Sp1, POU d omain, CCAAT enhancer binding protein, and several other transcription factors as regulators of expression of keratinocyte genes.