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Science 17 November 1989:
Vol. 246. no. 4932, pp. 922 - 926
DOI: 10.1126/science.2530632
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Articles

Science, Vol 246, Issue 4932, 922-926
Copyright © 1989 by American Association for the Advancement of Science

articles

Cognate DNA binding specificity retained after leucine zipper exchange between GCN4 and C/EBP

P Agre, PF Johnson, and SL McKnight

Howard Hughes Research Laboratories, Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210.

Both C/EBP and GCN4 are sequence-specific DNA binding proteins that control gene expression. Recent evidence implicates C/EBP as a transcriptional regulator of genes involved in lipid and carbohydrate metabolism. The C/EBP protein binds avidly to the dyad symmetric sequence 5'-ATTGCGCAAT-3'; GCN4 regulates the transcription of genes that control amino acid biosynthesis in yeast, and binds avidly to the dyad symmetric sequence 5'-ATGA(G/C)TCAT-3'. Both C/EBP and GCN4 bind DNA via the same structural motif. This motif has been predicted to be bipartite, consisting of a dimerization interface termed the "leucine zipper" and a DNA contact surface termed the "basic region." Specificity of DNA binding has been predicted to be imparted by the basic region. As a test of this hypothesis, recombinant proteins were created wherein the basic regions and leucine zippers of GCN4 and C/EBP were reciprocally exchanged. In both of the recombinant polypeptides, DNA binding specificity is shown to track with the basic region.


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