The promoter of mouse transcription repressor bach1 is regulated by Sp1 and trans-activated by Bach1.
The Maf recognition element (MARE) is regulated by both activators and repressors. Bach1 and Bach2 repress MARE-dependent transcription by forming heterodimers with Maf-related oncoproteins. In order to gain an understanding of the regulation of bach1 gene expression, we analyzed the structure of the mouse bach1 gene. Comparison of the exon-intron structure of the bach1 gene with those of other NF-E2-related genes indicated that bach1 and bach2 constitute an evolutionarily distinct subfamily among bZip factors. The bach1 promoter region contains two GC boxes that are important for its basal activity and are bound by Sp1 in K562 cell extracts. In addition, we found an evolutionarily conserved MARE-like element located downstream of the transcription initiation site. Deletion of this element resulted in a higher promoter activity in K562 cells. Bach1 trans-activated its own promoter depending on the presence of the MARE-like element in co-transfection assays. However, Bach1 did not bind to the MARE-like element in electrophoretic mobility shift assays (EMSA). These results suggest that Bach1 activates its own promoter indirectly by inhibiting the putative repressor. Such a positive feedback regulation by the repressor Bach1 may play an important role in maintaining the expression of Bach1 while consolidating repression of other genes with MARE.
Sun
J
J
Department of Biochemistry, Hiroshima University School of Medicine, Kasumi Hiroshima 734-8551, Japan.
Muto
A
A
Hoshino
H
H
Kobayashi
A
A
Nishimura
S
S
Yamamoto
M
M
Hayashi
N
N
Ito
E
E
Igarashi
K
K
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites / Q000502:physiology; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D051856:Fanconi Anemia Complementation Group Proteins; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology
C102108:BACH1 protein, human; C491123:BACH2 protein, human; C486316:Bach1 protein, mouse; C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; C495607:MAF protein, human; C495608:Maf protein, mouse; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors