BS69, a corepressor interacting with ZHX1, is a bifunctional transcription factor
BS69, a corepressor interacting with ZHX1, is a bifunctional transcription factor
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DOI：
10.2741/2197
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Miyamoto, Kaoru
中科院分区：
文献类型：
--
作者：
Ogata-Kawata, Hiroko;Yamada, Kazuya;Miyamoto, Kaoru
辅抑制因子BS69与ZHX1相互作用，ZHX1是ZHX家族的成员，具有锌指和同源盒。在大鼠中，我们已经确定了四种形式的剪接变体，BS69 α, BS69 β， BS69 γ和BS69 δ。根据氨基酸序列，BS69 α与人类的同源物相一致。BS69 β和BS69 γ含有一个由大鼠BS69基因外显子11b编码的56个氨基酸的新区域。BS69 gamma和BS69 delta都缺少基因外显子3编码的区域。尽管这四种变体在大鼠中普遍表达，但在小鼠和大鼠中检测到具有外显子11b的转录本，而在人类中则没有。BS69与ZHX1的PxLxP基序相互作用需要一个共同的c端MYND结构域。虽然BS69最初被发现是作为与ZHX1相互作用的协同抑制因子，但BS69也被发现在HEK293细胞中作为转录激活因子，其中激活需要BS69的MYND结构域。BS69与不能与BS69相互作用的突变体ZHX1共转染，导致BS69的转录激活增加，表明BS69介导的转录激活受到ZHX1的抑制。相比之下，BS69在COS-7和CV-1细胞中表现出转录抑制，并且抑制区域被定位到BS69 β的n端。野生型和突变型ZHX1对BS69的抑制均无影响，提示BS69在COS-7和CV-1细胞中介导的抑制可能需要细胞中除ZHX1外的辅助因子。因此，我们的研究结果表明，BS69可能作为转录抑制因子或转录激活因子发挥作用，这取决于其调控伙伴。
Corepressor BS69 interacts with ZHX1, a member of the ZHX family having zinc-fingers and homeoboxes. In the rat, we have identified four forms of splicing variants, BS69 alpha, BS69 beta, BS69 gamma, and BS69 delta. Based on the amino acid sequence, BS69 alpha corresponded to the human orthologue. BS69 beta and BS69 gamma contain a novel 56 amino acid region encoded by the exon 11b of the rat BS69 gene. Both BS69 gamma and BS69 delta lacked a region encoded by exon 3 of the gene. Although all four variants were ubiquitously expressed in rats, the transcripts having the exon 11b were detected in mice and rats but not in humans. A common C-terminal MYND domain of BS69 was required for the interaction with PxLxP motif of ZHX1. Although BS69 was originally found as a corepressor interacting with ZHX1, BS69 was also found to function as a transcriptional activator in HEK293 cells, in which the activation required the MYND domain of BS69. Co-transfection of BS69 with a mutant form of ZHX1, which cannot interact with BS69, led to increase the transcriptional activation of BS69, suggesting that transcriptional activation mediated by BS69 is suppressed by ZHX1. In contrast, BS69 showed transcriptional repression in COS-7 and CV-1 cells and the repression domain was mapped to the N-terminus of BS69 beta. Both the wild type and mutant form of ZHX1 had no effect on the BS69 repression, suggesting that the repression mediated by BS69 in COS-7 and CV-1 cells may require a cofactor other than ZHX1 in the cells. Therefore, our results suggest that BS69 may function either as a transcriptional repressor or as a transcriptional activator depending on its regulatory partner.