Multivalent DNA Binding Complex Generated by Small Maf and Bach1 as a Possible Biochemical Basis for β-Globin Locus Control Region Complex*
- Kazuhiko Igarashi‡§‖,
- Hideto Hoshino‡‖,
- Akihiko Muto‡‖,
- Naruyoshi Suwabe‡,
- Shinichi Nishikawa¶,
- Hiromitsu Nakauchi‡ and
- Masayuki Yamamoto‡
- From the ‡Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tenno-dai 1-1-1, Tsukuba 305, Japan and the ¶Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606, Japan
Abstract
The human β-globin locus control region (LCR) is required to properly regulate chromatin domain opening, replication timing, and globin gene activation. The LCR contains multiple NF-E2 sites (Maf recognition elements, MAREs) that allow the binding of various basic leucine zipper (bZip) proteins like p45 NF-E2, Nrf1, Nrf2, Bach1, and Bach2, in some cases as obligate heterodimers with a small Maf protein. In addition to the bZip domain, the Bach proteins bear a BTB/POZ domain, which has been implicated in the regulation of chromatin structure. We show here that Bach1 is highly expressed in hematopoietic cells and constitutes one of the two MARE-binding activities in murine erythroleukemic (MEL) cells. We further demonstrate that Bach1/MafK heterodimers interact with each other through the BTB domain, generating a multimeric and multivalent DNA binding complex. These results strongly implicate Bach1/MafK heterodimer as an architectural transcription factor that mediates interactions among multiple MAREs. Such a factor could then provide a model for assembly of the theoretical β-globin LCR “holocomplex.” Other BTB domain proteins have already been demonstrated to be involved in remodeling chromatin, and thus this class of proteins likely promote the formation of nucleoprotein complexes required to establish the architecture of regulatory domains.
Footnotes
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↵* This work was supported by the International Scientific Research Program and grants-in-aid from the Ministry of Education, Science, Sport, and Culture of Japan, and grants from the Japanese Society for the Promotion of Science (RFTF), the Mochida Memorial Foundation, the Ciba-Geigy Foundation Japan, and the Naito Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ To whom correspondence should be addressed. Tel.: 81-22-717-8086; Fax: 81-22-717-8090.
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↵‖ Present address: Dept. of Biochemistry, Tohoku University School of Medicine, Seiryo-machi 2-1, Sendai 980-8575, Japan.
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↵1 The abbreviations used are: LCR, locus control region; BTB domain, bric-a-brac, tramtrack, and broad complex domain; MARE, Maf recognition element; EMSA, electrophoretic mobility shift assay; RT-PCR, reverse transcriptase-polymerase chain reaction; HPRT, hypoxanthine phosphoribosyltransferase; ES, embryonic stem; Flk-1, fetal liver kinase-1; bp, base pair(s).
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↵2 H. Hoshino, A. Muto, and K. Igarachi, unpublished data.
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↵3 N. Suwabe and M. Yamamoto, manuscript in preparation.
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- Received January 29, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
