A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through the BTB/POZ domain.
Bach2 is a B-cell- and neuron-specific transcription repressor that forms heterodimers with the Maf-related oncoproteins. We show here that Bach2 activates transcription by interacting with its novel partner MAZR. MAZR was isolated by the yeast two-hybrid screen using the BTB/POZ domain of Bach2 as bait. Besides the BTB/POZ domain, MAZR possesses Zn finger motifs that are closely related to those of the Myc-associated Zn finger (MAZ) protein. MAZR mRNA was coexpressed with Bach2 in B cells among hematopoietic cells and in developing mouse limb buds, suggesting a cooperative role for MAZR and Bach2 in these cells. MAZR forms homo- and hetero-oligomers with Bach2 through the BTB domain, which oligomers bind to guanine-rich sequences. Unlike MAZ, MAZR functioned as a strong activator of the c-myc promoter in transfection assays with B cells. However, it does not possess a typical activation domain, suggesting a role for it as an unusual type of transactivator. The fgf4 gene, which regulates morphogenesis of limb buds, contains both guanine-rich sequences and a Bach2 binding site in its regulatory region. In transfection assays using fibroblast cells, the fgf4 gene was upregulated in the presence of both MAZR and Bach2 in a BTB/POZ domain-dependent manner. The results provide a new perspective on the function of BTB/POZ domain factors and indicate that BTB/POZ domain-mediated oligomers of transcription factors may serve as combinatorial codes for gene expression.
Kobayashi
A
A
Department of Biochemistry, Tohoku University School of Medicine, Sendai 980-8575, Japan.
Yamagiwa
H
H
Hoshino
H
H
Muto
A
A
Sato
K
K
Morita
M
M
Hayashi
N
N
Yamamoto
M
M
Igarashi
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D002460:Cell Line; D004268:DNA-Binding Proteins; D005314:Embryonic and Fetal Development / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
C491123:BACH2 protein, human; C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C485875:Zfp278 protein, mouse; C076035:c-MYC-associated zinc finger protein