Structure and evolution of the human SPRR3 gene: Implications for functionand regulation

SPRR3, a member of the SPRR family of cornified envelope precursor proteins , is expressed in oral and esophageal epithelia, where it is strictly linke d to keratinocyte terminal differentiation. This gene is characterized by i ntragenic duplications that have created the characteristic proline-rich re peats in the coding sequence, an alternative noncoding exon, and a 200-bp p olypyrimidine tract in the promoter region, Mutational analysis of the prom oter region and transient transfection in normal human keratinocytes showed that in addition to the polypyrimidine tract, multiple regulatory elements are involved in differentiation-specific expression. These elements includ e a high-affinity Ets binding site bound by ESE-1, an AP-1 site (TRE) recog nized by the Jun/Fos family of transcription factors, and an ATF/CRE bound by Jun/Foe and ATF factors. The repositioning of the SPRR3 Ets binding site during evolution has a major effect on the relative contribution of this s ite to promoter activity. (C) 1999 Academic Press.