title: Leucine zippers of fos, jun and GCN4 dictate dimerization specificity and thereby control DNA binding.
abstract: The products of the fos and jun protooncogenes form a stable heterodimer which binds to the TPA-responsive element (TRE) TGACTCA with high affinity. These two proteins, together with the yeast GCN4 protein, belong to a growing family of transcription factors, including FosB, Fra1, JunB and JunD, whose members share a highly conserved DNA-binding domain. This domain is composed of two structures: a basic motif, which is thought to bind directly to DNA; and a leucine zipper, which provides a dimerization interface. Although this domain is highly conserved in Fos, Jun and GCN4, each of these three proteins has very different relative affinities for the TRE. To understand these differences, we used 'domain-swapping' experiments designed to test the relative contributions of the basic motif and the leucine zipper to TRE-binding affinity. Here we show that fos, jun and GCN4 have different affinities for the TRE due to differences in the hetero- or homo-dimerization capacity of their leucine zipper domains; the basic motifs of these three proteins have comparable DNA binding potential. These results indicate that leucine zippers control the types of protein complexes which can associate with a TRE and regulate gene expression.
authors.affiliation: Department of Biochemistry, New York University Medical Center, New York 10016.
authors.forename: T
authors.initials: T
authors.lastname: Kouzarides
authors.forename: E
authors.initials: E
authors.lastname: Ziff
mesh_terms: D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D004247:DNA