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Hormone Research Institute and Department of Biochemistry and Biophysics, University of California San Francisco, California 94143-0534
Address requests for reprints to: Dr. William J. Rutter, Hormone Research Institute, University of California, San Francisco, California 94143-0534.
Abstract
Cell-specific expression of the insulin gene is dependent on a conserved 8-basepair sequence, GCCATCTG, present in two copies in the 5' flanking DNA of the rat insulin I gene (Nir and Far elements). A protein factor with well characterized binding affinities binds to this sequence and is unique to the nuclei of insulin-producing cells. Using the Nir element as a probe to screen a hamster insulinoma cDNA expression library, we cloned two cDNA inserts that encode two related helix-loop-helix DNAbinding proteins: Syrian hamster Pan-1 (shPan-1) and Syrian hamster Pan-2 (shPan-2). These clones have minimal differences from the previously reported human E47/E12 and rat PAN (rPan) DNAbinding proteins. In vitro translated protein products of both clones bound the insulin gene promoter Nir and Far elements as well as the E2 elements of the µ heavy chain and 
light chain immunoglobulin genes. Treating insulinoma cell nuclear extract with antiserum selectively directed to each of the two shPan proteins demonstrated the presence of each form of shPan in separate DNA-binding complexes, which together form the previously described, cellspecific, Nir element-binding complex. We conclude that shPan-1 and shPan-2 are the hamster homologs of the ubiquitous E47/E12 and rPan proteins, but form parts of distinct DNA-binding complexes apparently found only in the nuclei of insulin-producing cells.
FOOTNOTES
This work was supported by NIH Grant DK-21344, NIH Fellowship DK-08359-02 (to M.S.G.), a Juvenile Diabetes Foundation fellowship (to M.A.B.), NIH Fellowship GM-12441 (to C.N.), and a Juvenile Diabetes Foundation grant (to L.G.M.).
* Present address: Department of Biochemistry, University of California, Riverside, California 92521.
Present address: Departments of Medicine and Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Received for publication September 17, 1990. Revision received November 16, 1990. Accepted for publication November 17, 1990.
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