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Novel Insulin Promoter- and Enhancer-Binding Proteins That Discriminate between Pancreatic - and β-Cells

Department of Microbiology, University of Umea S-901 87 Umea, Sweden

Address requests for reprints to: Dr. Thomas Edlund, Department of Microbiology, University of Umea, S-901 87 Umea, Sweden.

Abstract

In the mouse insulin is first detected on embryonic day 12 (e12) in a subpopulation of the cells that on e10 start to produce glucagon. During the continued embryonic development, the number of cells that coexpress the two hormones is gradually decreased, and in adults the expression of these two hormone genes is segregated to the β- and -cells. To begin to understand the process of terminal differentiation that restricts insulin gene expression to β-cells, we have assayed for the presence of nuclear proteins that interact with transcriptional regulatory sequences of the rat insulin I gene in pancreatic -and β-cell lines. All except one of the previously identified insulin enhancer-binding proteins were found to be present in both cell types. A new insulin promoter-binding protein, IPF1, which was present in β-cells but absent in -cells, was indentified. The β-cell specificity of IPF1 implies that the insulin promoter is involved in the restriction of insulin gene expression to the β-cells. The binding sites for IPF1 and the β-cell-specific enhancer-binding protein IEF2 are both recognized by the previously isolated homeodomain-containing LIM protein lsl-1, but these three proteins were all shown to be different entities.

FOOTNOTES

This work was supported by grants from the MFR, NFR, and STUF (to T.E.).

Received for publication January 21, 1991. Revision received April 9, 1991. Accepted for publication April 12, 1991.

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