MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination.
ME1a1, a 16-base-pair nuclear factor binding site residing between the c-MYC P1 and P2 transcription initiation sites, is required for P2 activity. A cDNA encoding a 477-amino acid zinc finger protein designated MAZ (MYC-associated zinc finger protein) was cloned from a HeLa lambda gt11 library by screening with a concatamerized ME1a1 binding site probe. In addition to six potential zinc fingers of the Cys2His2 type, MAZ contains an amino-terminal proline-rich domain and several polyalanine tracts. Its mRNA was present in all human tissues tested except for kidney, as a doublet of approximately 2.5 and 2.7 kilobases, along with differentially expressed minor species. MAZ bound specifically to the wild-type ME1a1 sequence but not to a ME1a1 mutant that also failed to yield P2 activity. When expressed as a fusion protein in a pMAL-c vector, MAZ binds with specificity to a GA box sequence (GGGAGGG) found in the c-MYC P2 promoter, to the P2 attenuator region within the gene's first exon, and to a related sequence involved in the transcriptional termination of the C2 gene. MAZ may encode a transcription factor with dual roles in transcription initiation and termination.
Bossone
S A
SA
Department of Pathology, State University of New York, Stony Brook 11794.
Asselin
C
C
Patel
A J
AJ
Marcu
K B
KB
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D005091:Exons; D015723:Gene Library; D016259:Genes, myc; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015183:Restriction Mapping; D013728:Terminator Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; D015500:Chloramphenicol O-Acetyltransferase