A conserved region adjacent to the basic domain is required for recognition of an extended DNA binding site by Maf/Nrl family proteins.
The c-maf proto-oncogene and the neural retina specific gene nrl encode members of a subfamily of bZIP proteins that form heterodimers with Fos and Jun. We have determined the DNA binding specificities of various homo- and heterodimeric combinations among Nrl, Maf, Fos and Jun. Fos-Jun heterodimers and Jun homodimers bound to a palindromic TGAC(G)TCA recognition sequence as previously demonstrated. Maf and Nrl homodimers also bound to palindromic recognition sites with the consensus sequence TGC(N)6-7GCA. Fos-Nrl, Jun-Nrl and Fos-Maf heterodimers bound to nonpalindromic recognition sequences with the consensus sequence TGAC(N)3-4GCA. These results indicate that Nrl and Maf have a DNA binding specificity distinct from that of Fos and Jun, and that each subunit in the dimer independently recognizes one half of the recognition sequence. This allows combinatorial determination of target gene specificity. Specific recognition of the extended DNA binding sequence by Maf requires an ancillary DNA binding region on the amino terminal side of the basic domain that is conserved among Maf/Nrl family members. Thus, heterodimer formation among distantly related bZIP family members can generate novel DNA binding specificities and the addition of an auxiliary DNA binding domain to the simple bZIP motif can facilitate the recognition of extended binding sites.
Kerppola
T K
TK
Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
Curran
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005136:Eye Proteins; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf; D011994:Recombinant Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D051257:Proto-Oncogene Proteins c-maf; D011994:Recombinant Proteins; D004247:DNA