The Promoter of Mouse Transcription Repressor bachl Is Regulated by Spl and Trans-Activated by Bachl

Abstract

The Maf recognition element (MARE) is regulated by both activators and repressors. Bachl and Bach2 repress MARE-dependent transcription by forming heterodimers with Maf-related oncoproteins. In order to gain an understanding of the regulation of bachl gene expression, we analyzed the structure of the mouse bachl gene. Comparison of the exon-intron structure of the bachl gene with those of other NF-E2-related genes indi-cated that bachl and bach2 constitute an evolutionarily distinct subfamily among bZip factors. The bachl promoter region contains two GC boxes that are important for its basal activity and are bound by Spl in K562 cell extracts. In addition, we found an evo-lutionarily conserved MARE-like element located downstream of the transcription initi-ation site. Deletion of this element resulted in a higher promoter activity in K562 cells. Bachl trans-activated its own promoter depending on the presence of the MARE-like element in co-transfection assays. However, Bachl did not bind to the MARE-like ele-ment in electrophoretic mobility shift assays (EMSA). These results suggest that Bachl activates its own promoter indirectly by inhibiting the putative repressor. Such a posi-tive feedback regulation by the repressor Bachl may play an important role in main-taining the expression of Bachl while consolidating repression of other genes with MARE.