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Molecular and Cellular Biology, March 2000, p. 1733-1746, Vol. 20, No. 5
Department of Biochemistry, Tohoku University School of
Medicine, Sendai 980-8575,1 Center for
Tsukuba Advanced Research Alliance and Institute of Basic Medical
Sciences, University of Tsukuba, Tsukuba
305-8577,2 and Department of
Biochemistry, Hiroshima University School of Medicine, Hiroshima
734-8551,3 Japan
Received 27 August 1999/Returned for modification 28 September
1999/Accepted 29 November 1999
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.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
A Combinatorial Code for Gene Expression Generated
by Transcription Factor Bach2 and MAZR (MAZ-Related Factor) through the
BTB/POZ Domain
*
Corresponding author. Mailing address: Department of
Biochemistry, Hiroshima University School of Medicine, Kasumi 1-2-3, Hiroshima 734-8551, Japan. Phone: 81-82-257-5135. Fax: 81-82-257-5139. E-mail: igarak{at}mcai.med.hiroshima-u.ac.jp.
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