GENOMIC ORGANIZATION AND EXPRESSION OF A HUMAN GENE FOR MYC-ASSOCIATED ZINC-FINGER PROTEIN (MAZ)

We have cloned and characterized the genomic structure of the human ge ne for Myc-associated zinc finger protein (MAZ), which is located on c hromosome 16p11.2. This gene is transcribed as an mRNA of 2.7 kilobase s (kb) that encodes a 60-kDa MAZ protein. A 40-kb cosmid clone was iso lated that includes the promoter, five exons, four introns, and one 3' -untranslated region. All exon-intron junction sequences conform to th e GT/AG rule. The promoter region has features typical of a housekeepi ng gene: a high G + C content (88.44%); a high frequency of CpG dinucl eotides, in particular within the region 0.5 kb upstream of the site o f initiation of translation; and the absence of canonical TATA and CAA T boxes. An S1 nuclease protection assay demonstrated the presence of multiple sites for initiation of transcription around a site 174 nucle otides (nt) upstream of the ATG codon and such expression was reflecte d by the promoter activity of a MAZ promoter/CAT (chloramphenicol acet yltransferase) reporter gene. Cis-acting positive and negative element s controlling basal transcription of the human MAZ gene were found fro m nucleotides (nt) -383 to -248 and nt -2500 to -948. Moreover, positi ve and negative autoregulatory elements were also identified in the re gions from nt -248 to -189 and from nt -383 to -248 after co-transfect ion of HeLa cells with plasmids that carried the MAZ promoter/CAT cons truct and the MAZ-expression vector. Our results indicate that the 5'- end flanking sequences are responsible for the promoter activities of the MAZ gene.