IPF1, a homeodomain-containing transactivator of the insulin gene, was cloned and characterized in this study. IPF1 is selectively expressed in β-cells of the adult mouse pancreas and binds to and transactivates the insulin promoter, suggesting a direct role in β-cell-specific insulin gene expression. In embryos, IPF1 expression begins before hormone gene expression and is restricted to the dorsal and ventral walls of the primitive foregut, where the pancreas will later develop. The expression pattern and transactivation ability of IPF1 indicate its involvement in the regionalization of the primitive gut endoderm and the maturation of pancreatic β-cells. IPF1 is a novel mammalian homeodomain-containing protein that, along with XlHbox8 from Xenopus and Htr-A2 from the leech, defines a specific class of homeotic proteins. The homeodomains of these proteins are highly homologous, with a unique histidine at position 45 of helix 3. IPF1 is only expressed in β-cells of the adult mouse pancreas and is not present in glucagon-producing α-cells. IPF1 binds to the P1 promoter site and is capable of transactivating the insulin promoter, supporting its role in β-cell-specific insulin gene expression. In mouse embryos, IPF1 expression is initiated prior to hormone gene expression and is restricted to the dorsal and ventral walls of the primitive foregut. IPF1 expression is restricted to the sites where the dorsal and ventral pancreas will start to evaginate. IPF1 is selectively expressed in pancreatic progenitor cells in early embryos, and its expression is correlated with the commitment of the primitive foregut endoderm to a pancreatic fate. IPF1 is not expressed in non-β-cells and is only found in β-cells of the adult pancreas. IPF1 is selectively expressed in the β-cells of the adult pancreas and is not present in glucagon-producing α-cells. IPF1 is not co-expressed with glucagon in β-cells, suggesting that β-cells and α-cells develop independently. IPF1 is also selectively expressed in the pancreatic progenitor cells in early embryos, and its expression is correlated with the commitment of the primitive foregut endoderm to a pancreatic fate. IPF1 is a homeodomain-containing protein that binds to the P1 promoter site and is capable of transactivating the insulin promoter. IPF1 is selectively expressed in β-cells of the adult pancreas and is not present in glucagon-producing α-cells. IPF1 is not co-expressed with glucagon in β-cells, suggesting that β-cells and α-cells develop independently. IPF1 is also selectively expressed in the pancreatic progenitor cells in early embryos, and its expression is correlated with the commitment of the primitive foreIPF1, a homeodomain-containing transactivator of the insulin gene, was cloned and characterized in this study. IPF1 is selectively expressed in β-cells of the adult mouse pancreas and binds to and transactivates the insulin promoter, suggesting a direct role in β-cell-specific insulin gene expression. In embryos, IPF1 expression begins before hormone gene expression and is restricted to the dorsal and ventral walls of the primitive foregut, where the pancreas will later develop. The expression pattern and transactivation ability of IPF1 indicate its involvement in the regionalization of the primitive gut endoderm and the maturation of pancreatic β-cells. IPF1 is a novel mammalian homeodomain-containing protein that, along with XlHbox8 from Xenopus and Htr-A2 from the leech, defines a specific class of homeotic proteins. The homeodomains of these proteins are highly homologous, with a unique histidine at position 45 of helix 3. IPF1 is only expressed in β-cells of the adult mouse pancreas and is not present in glucagon-producing α-cells. IPF1 binds to the P1 promoter site and is capable of transactivating the insulin promoter, supporting its role in β-cell-specific insulin gene expression. In mouse embryos, IPF1 expression is initiated prior to hormone gene expression and is restricted to the dorsal and ventral walls of the primitive foregut. IPF1 expression is restricted to the sites where the dorsal and ventral pancreas will start to evaginate. IPF1 is selectively expressed in pancreatic progenitor cells in early embryos, and its expression is correlated with the commitment of the primitive foregut endoderm to a pancreatic fate. IPF1 is not expressed in non-β-cells and is only found in β-cells of the adult pancreas. IPF1 is selectively expressed in the β-cells of the adult pancreas and is not present in glucagon-producing α-cells. IPF1 is not co-expressed with glucagon in β-cells, suggesting that β-cells and α-cells develop independently. IPF1 is also selectively expressed in the pancreatic progenitor cells in early embryos, and its expression is correlated with the commitment of the primitive foregut endoderm to a pancreatic fate. IPF1 is a homeodomain-containing protein that binds to the P1 promoter site and is capable of transactivating the insulin promoter. IPF1 is selectively expressed in β-cells of the adult pancreas and is not present in glucagon-producing α-cells. IPF1 is not co-expressed with glucagon in β-cells, suggesting that β-cells and α-cells develop independently. IPF1 is also selectively expressed in the pancreatic progenitor cells in early embryos, and its expression is correlated with the commitment of the primitive fore