Transcriptional co-activator activity of SYT is negatively regulated by BRM and Brg1

Transcriptional co-activator activity of SYT is negatively regulated by BRM and Brg1
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DOI:
10.1111/j.1356-9597.2004.00737.x
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发表时间:
2004-05-01
期刊:
影响因子:
2.1
通讯作者:
Ohta, T
Ohta, T
中科院分区:
生物学4区
文献类型:
--
作者:
Ishida, M;Tanaka, S;Ohta, T

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滑膜肉瘤中发现的t(X;18)(p11.2;q11.2)易位导致18号染色体上的SYT基因与X号染色体上的SSX基因融合。尽管SYT-SSX融合蛋白可能引发滑膜肉瘤的发生,但SYT、SSX和SYT-SSX基因的生物学功能尚不清楚。对Gal4 DNA结合域融合蛋白构建体的转染表明,SYT蛋白在c端区域起转录共激活剂的作用,其活性通过n端被抑制。SYT的n端70个氨基酸不仅与BRM结合,还与Brg1结合,两者都是SWI/SNF染色质重塑复合物的亚基。在此,我们研究了BRM和Brg1对SYT活性的抑制作用。SYT转录共激活因子活性的负调控依赖于蛋白质复合物中BRM和Brg1的atp水解。这表明SWI/SNF蛋白复合物通过染色质重塑活性调节SYT活性。
The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in the fusion of the SYT gene on chromosome 18 to the SSX gene on chromosome X. Although the SYT-SSX fusion proteins may trigger synovial sarcoma development, the biological functions of SYT, SSX and SYT-SSX genes are unclear. Transfections of Gal4 DNA binding domain fusion protein constructs demonstrate that SYT protein acts as a transcriptional co-activator at the C-terminal domain and that the activity is repressed through the N-terminus. The N-terminal 70 amino acids of SYT bind not only to BRM, but also to Brg1, both of which are subunits of SWI/SNF chromatin remodelling complexes. Here, we have investigated the functions of BRM and Brg1 on the repression of SYT activity. The negative regulation of SYT transcriptional co-activator activity is dependent on the ATP-hydrolysis of BRM and Brg1 in the protein complexes. This indicates that the SWI/SNF protein complexes regulate SYT activity using the chromatin remodelling activity.