Characterization of BHC80 in BRAF-HDAC complex, involved in neuron-specific gene repression
Characterization of BHC80 in BRAF-HDAC complex, involved in neuron-specific gene repression
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DOI：
10.1016/j.bbrc.2004.07.163
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发表时间：
2004-09-17
影响因子：
3.1
通讯作者：
Baba, T
中科院分区：
文献类型：
--
作者：
Iwase, S;Januma, A;Baba, T
BRAF-HDAC复合体(BHC)含有包括BHC80在内的6种成分，并在非神经细胞中介导对其神经元特异性基因的静息依赖性转录抑制。在这项研究中，我们研究了BHC80在小鼠组织和人类培养细胞中的功能作用(S)。小鼠BHC80的两种亚型主要存在于中枢神经系统和生精细胞中。人类培养的细胞也含有两种BHC80亚型。免疫组织化学分析显示，小鼠BHC80阳性细胞位于小鼠小脑和海马神经元的胞核中。含有PHD锌指结构域的人BHC80的C末端区域能够直接与BHC的其他五个组分中的每一个结合，并能够组织BHC介导转录抑制。此外，人BHC80的两种异构体通过减少与HDAC1和HDAC2的结合而相互区别，尽管存在PHD指状域。这些结果表明，BHC80可能是神经细胞和非神经细胞中BHC的支架蛋白。并提出了BHC80在精子发生中的可能作用。(C)2004 Elsevier Inc.保留所有权利。
BRAF-HDAC complex (BHC) has been shown to contain six components, including BHC80, and to mediate REST-dependent transcriptional repression of it neuron-specific genes in non-neuronal cells. In this study, we have examined the functional role(s) of BHC80 in mouse tissues and human cultured cells. Two isoforms of mouse BHC80 were predominantly present in the central nervous system and spermatogenic cells. Human cultured cells also contained two isoforms of BHC80. lmmunohistochemical analysis showed the presence of mouse BHC80 in the nucleus of neuronal cells in the hippocampus and cerebellum. The C-terminal region of human BHC80 containing PHD zinc-finger domain was capable of binding directly to each of five other components of BHC, and of organizing BHC mediating transcriptional repression. Moreover, two isoforms of human BHC80 were distinguished from each other by reduced binding to HDAC1 and HDAC2, despite the presence of the PHD finger domain. These results suggest that BHC80 presumably serves as a scaffold protein in BHC in neuronal as well as non-neuronal cells. A possible role of BHC80 in spermatogenesis is also suggested. (C) 2004 Elsevier Inc. All rights reserved.