Hoshino Hideto, Nishino Tomonori George, Tashiro Satoshi, Miyazaki Masaya, Ohmiya Yoshihiro, Igarashi Kazuhiko, Horinouchi Sueharu, Yoshida Minoru
CREST Research Project, Japan Science and Technology Corp., Saitama 332-0012, Japan.
J Biochem. 2007 May;141(5):719-27. doi: 10.1093/jb/mvm073. Epub 2007 Mar 23.
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.
Bach2是BTB-碱性区域亮氨酸拉链因子家族的成员,可抑制由佛波酯反应元件、Maf识别元件(MARE)和抗氧化反应元件介导的转录活性。最近有报道称,在氧化应激条件下,Bach2会在早幼粒细胞白血病(PML)小体周围形成核灶,并特异性抑制PML小体周围的转录。在此我们报道,维甲酸和甲状腺激素受体沉默介质(SMRT)及组蛋白去乙酰化酶4(HDAC4)的表达会增强核基质中Bach2核灶的形成。SMRT介导HDAC4与Bach2结合,而HDAC4则促进Bach2在核灶中的滞留。划痕转录标记和共聚焦图像的三维重建显示,Bach2核灶及其周围的转录受到抑制。实际上,当与SMRT和HDAC4共表达时,Bach2会结合MARE并抑制染色体整合的MARE驱动报告基因的表达。我们的观察结果表明,SMRT和HDAC4在哺乳动物细胞核中Bach2的核滞留和核灶形成过程中均发挥重要作用,这可能有助于局部转录抑制。