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Molecular and Cellular Biology, March 2000, p. 1733-1746, Vol. 20, No. 5
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

Akira Kobayashi,1 Hironori Yamagiwa,2 Hideto Hoshino,1 Akihiko Muto,1 Kazushige Sato,1 Masanobu Morita,2 Norio Hayashi,1 Masayuki Yamamoto,2 and Kazuhiko Igarashi1,3,*

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.

* 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.

Molecular and Cellular Biology, March 2000, p. 1733-1746, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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