Journal of Biochemistry Advance Access originally published online on March 23, 2007
Journal of Biochemistry 2007 141(5):719-727; doi:10.1093/jb/mvm073
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© 2007 The Japanese Biochemical Society.
Co-repressor SMRT and Class II Histone Deacetylases Promote Bach2 Nuclear Retention and Formation of Nuclear Foci that are Responsible for Local Transcriptional Repression
1CREST Research Project, Japan Science and Technology Corp., Saitama 332-0012; 2Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657; 3Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198; 4Department of Biomedical Chemistry, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Hiroshima 734-8551; and 5National Institute of Advanced Industrial Science and Technology, Research Institute for Cell Engineering, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan
*To whom correspondence should be addressed. Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Tel: 048-467-9516, Fax: 048-462-4676, E-mail: yoshidam{at}riken.jp
Received February 23, 2007; Accepted February 26, 2007
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Abstract |
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Bach2 is a member of the BTB-basic region leucine zipper factor family and represses transcription activity directed by the TPA response element, the Maf recognition element (MARE) and the antioxidant-responsive element. Recently, it was reported that upon oxidative stress Bach2 forms nuclear foci surrounding the promyelocytic leukaemia (PML) bodies and specifically represses the transcription around the PML bodies. Here we report that expression of the silencing mediator of retinoid and thyroid receptor (SMRT) and histone deacetylase4 (HDAC4) enhances the formation of the Bach2 foci in the nuclear matrix. SMRT mediates the HDAC4 binding to Bach2, and HDAC4 facilitates the retention of Bach2 in the foci. Scratch transcription labelling and 3D-reconstruction from the confocal images demonstrated that transcription is suppressed in and around the Bach2 foci. Indeed, Bach2 bound MARE and repressed the expression from the chromosomally integrated MARE-driven reporter gene when co-expressed with SMRT and HDAC4. Our observations suggest that both SMRT and HDAC4 play an important role in nuclear retention and the Bach2 focus formation in the mammalian cell nucleus, which may contribute to the local transcription repression.
Key Words: Bach2, HDAC4, nuclear domain, SMRT, transcription repression
Abbreviations: CLS, cytoplasmic localization signal; ChIP, chromatin-immunoprecipitation; HDAC, histone deacetylase; LMB, leptomycin B; MAD body, matrix-associated deacetylase body; MARE, Maf recognition element; NES, nuclear export signal; PML, promyelocytic leukaemia; SMRT, silencing mediator of retinoid and thyroid receptor
Present addresses: Satoshi Tashiro, Research Institution for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Hiroshima 734-8551, Japan; Kazuhiko Igarashi, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
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