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Sturctural Organization and Expression of Human Gene for Myc-associated Zinc Finger Protein (MAZ): Jun SONG, Chie KOGA and Kazunari K. YOKOYAMA (Tsukuba Life Science Center, RIKEN, Japan)

We have cloned and characterized the genomic structure of the human gene for Myc-associated zinc finger protein (MAZ), which is located on chromosome 16p11.2. This gene is transcribed as an mRNA of 2.7 kb that encodes a 60-kDa MAZ protein. The cloned MAZ gene spans a 40-kb region that includes the promoter, five exons, four introns and one 3'-untranslated region. Sequneces of all exon-intron junctions conform to the GT/AG rule. The promoter region has features typical of a housekeeping gene: a high G+C content (88.4%); a high frequency of CpG dinucleotides, in particular within the region 0.5 kb upstream of the site of initiation of translation; and the absence of canonical TATA and CAAT boxes. An S1 nuclease protection assay showed the presence of multiple sites for initiation of transcription around a site 174 nucleotides (nt) upstream of the ATG codon and such expression was reflected by the promoter activity of a MAZ promoter/CAT (chloramphenicol acetyltransferase) reporter gene. Cis-acting positive and negative elements controlling basal transcription of the human MAZ gene were found from nt -383 to -248 and nt -2500 to -948 (relative to the major transcription initiation site). Moreover, positive and negative autoregulatory elements were also identified in the regions from nt -248 to -189 and from nt -383 to -248 after cotransfection of HeLa cells with plasmids that carried the MAZ promoter/CAT construct and the MAZ-expression vector. Our results indicate that the 5'-end flanking sequences are responsible for the promoter activities of the MAZ gene.