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 line of a 1.4 kb cDNA encoding a new homeoprotein, IDX-1 (islet/duodenum homeobox-1), with close sequence similarity to the Drosophila melanogaster homeobox protein Antennapedia (Antp) and the Xenopus laevis endoderm-specific homeoprotein XlHbox8. Analyses of IDX-1 mRNA and protein in rat tissues show that IDX-1 is expressed in pancreatic islets and ducts and in the duodenum. In electrophoretic mobility shift assays IDX-1 binds to three sites in the 5' flanking region of the rat somatostatin gene. In co-transfection experiments IDX-1 transactivates reporter constructs containing somatostatin promoter sequences, and mutation of the IDX-1 binding sites attenuates transactivation. Reverse transcription-polymerase chain reaction of islet RNA using degenerate amplimers for mRNAs encoding homeoproteins indicates that IDX-1 is the most abundant of 12 different Antp-like homeodomain mRNAs expressed in adult rat islets. The pattern of expression, relative abundance and transcriptional 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.
Miller
C P
CP
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston.
McGehee
R E
RE
Habener
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D051943:Antennapedia Homeodomain Protein; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D006367:HeLa Cells; D018398:Homeodomain Proteins; D006801:Humans; D017403:In Situ Hybridization; D007515:Islets of Langerhans / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics*; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D051943:Antennapedia Homeodomain Protein; C497974:Antp protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein; D013004:Somatostatin