Tetramerization of SATB1 is essential for regulating of gene expression
Tetramerization of SATB1 is essential for regulating of gene expression
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SATB1的四聚化对于基因表达的调节至关重要
DOI：
10.1007/s11010-017-2964-6
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发表时间：
2017
影响因子：
4.3
通讯作者：
Zhou Hao
中科院分区：
文献类型：
--
作者：
Zheng Minying;Xing Wancai;Liu Yabing;Li Meng;Zhou Hao
富含特异性AT的序列结合蛋白1（SATB 1）在肿瘤发生中起着“基因组组织者”的作用。我们以前的研究表明SATB 1通过其N-末端泛素样结构域而不是PDZ结构域形成四聚体。在本研究中，我们的目的是说明这种寡聚化是否是至关重要的，其功能作为一个全球性的基因表达抑制体内。荧光素酶和GST下拉分析表明，破坏SATB 1的四聚体不仅影响启动子的活性，而且影响相互作用伴侣的招募。此外，我们开发了过表达SATB 1四聚体或STAB 1二聚体（KWN-AAA）的稳定细胞系，并监测了全局基因表达。基因表达谱分析显示，超过1000个基因显着上调或下调后，SATB 1或SATB 1（KWN-AAA）突变体的过表达。这些数据表明，SATB 1可能通过其不同的寡聚化状态调节基因表达。综上所述，我们推断SATB 1的寡聚化是其在不同生物过程中发挥功能的关键。
Special AT-rich sequence-binding protein 1 (SATB1) functions as a ‘genome organizer’ in tumorigenesis. Our previous report showed that SATB1 forms a tetramer through its N-terminal ubiquitin like domain rather than the proposed PDZ domain. In the present study, we aim to illustrate whether this oligomerization is critical to its function as a global repressor of gene expressionin vivo. Luciferase and GST pull-down assays demonstrated that disrupting SATB1’s tetramerization not only affects the activities of promoters but also influences the recruitment of interaction partners. Furthermore, we developed stable cell lines that overexpressed either the SATB1 tetramer or STAB1 dimer (KWN–AAA) and monitored global gene expression. Gene expression profiling revealed that over 1000 genes were significantly upregulated or downregulated upon the overexpression of SATB1 or the SATB1 (KWN–AAA) mutant. These data implied that SATB1 might regulate gene expression through its different oligomerization state. In conclusion, we inferred that the oligomerization of SATB1 is pivotal to its function of different biological processes.