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Originally published In Press as doi:10.1074/jbc.M107048200 on September 11, 2001

J. Biol. Chem., Vol. 276, Issue 46, 42632-42638, November 16, 2001
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Involvement of a Novel Zinc Finger Protein, MIZF, in Transcriptional Repression by Interacting with a Methyl-CpG-binding Protein, MBD2*

Masayuki Sekimata, Atsushi Takahashi, Akiko Murakami-SekimataDagger , and Yoshimi Homma§

From the Department of Biomolecular Sciences, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295 and the Dagger  School of Nursing, Miyagi University, Miyagi 981-3298, Japan

MBD2, a methyl-CpG-binding protein, is a component of the MeCP1 histone deacetylase (HDAC) complex and plays a critical role in DNA methylation-mediated transcriptional repression. To understand the molecular basis of the methylation-associated repression, we attempted to identify MBD2-interacting proteins by a yeast two-hybrid system. Using MBD2 as bait, we isolated a novel zinc finger protein, referred to as MIZF. A direct interaction between MBD2 and MIZF was confirmed by in vitro binding assays and immunoprecipitation experiments. Four of seven zinc fingers present in the C-terminal region of MIZF are required for binding with MBD2. The MIZF mRNA is expressed in all human tissues and cell lines examined. The subcellular localization of MIZF is distinct from that of MBD2, although both proteins co-localize in some areas of the nuclei; MIZF localizes diffusely in the nucleoplasmic region, whereas MBD2 preferentially localizes in major satellites. A reporter assay demonstrated that MIZF significantly abrogates transcriptional activities. This repression is attenuated by an HDAC inhibitor, trichostatin A, and is completely dependent on the interaction with MBD2. These results suggest that MIZF is abundantly present in cells and functions as a negative regulator of transcription by binding to MBD2 and recruiting HDAC-containing complexes.


* This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan.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.

§ To whom correspondence should be addressed. Tel.: 81-24-548-2111; Fax: 81-24-548-3041; E-mail: yoshihom@fmu.ac.jp.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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