Independent repression of a GC-rich housekeeping gene by Sp1 and MAZ involves the same cis-elements

The transcription factors Spl and MAZ ((M) under bar yc-(a) under bar ssoci ated (z) under bar inc finger protein) contain several zinc finger motifs, and each functions as both a positive and a negative regulator of gene expr ession. In this study, we characterized the extremely GC-rich promoter of t he human gene for MAZ, which is known as a housekeeping gene. Unique symmet rical motifs in the promoter region (nucleotides -383 to -334) were essenti al for the expression of the gene for MAZ, whereas an upstream silencer ele ment (nucleotides -784 to -612) was found to act in a position-dependent bu t orientation-independent manner. Spl and MAZ bound to the same cis-element s in the GC-rich promoter, apparently sharing DNA-binding sites. The relati ve extent of binding of Spl and MAZ to these cis-elements corresponded to t he extent of negative regulation of the expression of the gene for MAZ in v arious lines of cells. Furthermore, novel repressive do mains in both Spl ( amino acids 622-788) and MAZ (amino acids 127-292) were identified. Suppres sion by Spl and suppression by MAZ were independent phenomena; histone deac etylases were involved in the autorepression by MAZ itself, whereas DNA met hyltransferase 1 was associated with suppression by Spl. Our results indica te that both deacetylation and methylation might be involved in the regulat ion of expression of a single gene via the actions of different zinc finger proteins that bind to the same cis-elements.