IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene

EMBO J. 1994 Mar 1;13(5):1145-56.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antennapedia Homeodomain Protein
  • Base Sequence
  • Cell Line
  • DNA-Binding Proteins / genetics
  • Drosophila Proteins
  • Drosophila melanogaster / metabolism
  • Duodenum / metabolism*
  • Gene Expression Regulation
  • Gene Expression*
  • Genes, Homeobox*
  • HeLa Cells
  • Homeodomain Proteins*
  • Humans
  • In Situ Hybridization
  • Islets of Langerhans / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Promoter Regions, Genetic*
  • Protein Biosynthesis
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism
  • Rats
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Somatostatin / biosynthesis
  • Somatostatin / genetics*
  • Trans-Activators / biosynthesis
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Tumor Cells, Cultured
  • Xenopus laevis

Substances

  • Antennapedia Homeodomain Protein
  • Antp protein, Drosophila
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • pancreatic and duodenal homeobox 1 protein
  • Somatostatin

Associated data

  • GENBANK/U04833