Cognate DNA binding specificity retained after leucine zipper exchange between GCN4 and C/EBP.
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.
Agre
P
P
Howard Hughes Research Laboratories, Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210.
Johnson
P F
PF
McKnight
S L
SL
D000595:Amino Acid Sequence; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003850:Deoxyribonuclease I; D004926:Escherichia coli / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D005809:Genes, Regulator; D008969:Molecular Sequence Data; D009492:Neurospora crassa / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009710:Nucleotide Mapping; D011494:Protein Kinases; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA; D011494:Protein Kinases; D003850:Deoxyribonuclease I