IDX-1 - A NEW HOMEODOMAIN TRANSCRIPTION FACTOR EXPRESSED IN RAT PANCREATIC-ISLETS AND DUODENUM THAT TRANSACTIVATES THE SOMATOSTATIN GENE

We describe the cloning from a rat islet somatostatin-producing cell l ine of a 1.4 kb cDNA encoding a new homeoprotein, IDX-1 (islet/duodenu m homeobox-1), with close sequence similarity to the Drosophila melano gaster homeobox protein Antennapedia (Antp) and the Xenopus laevis end oderm-specific homeoprotein XlHbox8. Analyses of IDX-1 mRNA and protei n in rat tissues show that IDX-1 is expressed in pancreatic islets and ducts and in the duodenum. In electrophoretic mobility shift assays Z DX-1 binds to three sites in the 5' flanking region of the rat somatos tatin gene. In co-transfection experiments IDX-1 transactivates report er constructs containing somatostatin promoter sequences, and mutation of the IDX-1 binding sites attenuates transactivation. Reverse transc ription- polymerase chain reaction of islet RNA using degenerate ampli mers for mRNAs encoding homeoproteins indicates that IDX-1 is the most abundant of 12 different Antp-like homeodomain mRNAs expressed in adu lt rat islets. The pattern of expression, relative abundance and trans criptional regulatory activity suggests that IDX-1 may be involved in the regulation of islet hormone genes and in cellular differentiation in the endocrine pancreas and the duodenum.