The functional role of the CARM1-SNF5 complex and its associated HMT activity in transcriptional activation by thyroid hormone receptor
The functional role of the CARM1-SNF5 complex and its associated HMT activity in transcriptional activation by thyroid hormone receptor
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DOI：
10.1038/emm.2007.60
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发表时间：
2007-08-31
影响因子：
12.8
通讯作者：
Yoon, Ho-Geun
中科院分区：
文献类型：
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作者：
Choi, Hyo-Kyoung;Choi, Kyung-Chul;Yoon, Ho-Geun
我们研究了CARM 1-SNF 5复合物在T3依赖性转录激活中的功能和机制。利用特异性小干扰RNA（siRNA）敲除HeLa α 2细胞中的辅激活因子，我们发现辅激活因子相关的精氨酸甲基转移酶1（CARM 1）和SWI/SNF复合物组分5（SNF 5）对T3依赖的转录激活非常重要。CARM 1- SWI/SNF染色质重塑复合物是快速逆转H3-K9甲基化的机制。重要的是，针对CARM 1和/或SNF 5的siRNA处理增加了HMTase G9 a向1型脱碘酶（D1）启动子的募集，即使在T3的情况下也是如此。敲低CARM 1或SNF 5也抑制组蛋白macroH 2A的下调，这与转录激活相关。最后，通过siRNA敲低CARM 1和SNF 5损害了这些共激活因子与D1启动子的结合，表明CARM 1-SNF 5复合物在T3依赖性转录激活中的功能重要性。
We have investigated the function and mechanisms of the CARM1-SNF5 complex in T3-dependent transcriptional activation. Using specific small interfering RNAs (siRNA) to knock down coactivators in HeLa alpha 2 cells, we found that coactivator associated arginine methyltransferase 1 (CARM1) and SWI/SNF complex component 5 (SNF5) are important for T3-dependent transcriptional activation. The CARM1- SWI/SNF chromatin remodeling complex serves as a mechanism for the rapid reversal of H3-K9 methylation. Importantly, siRNA treatment against CARM1 and/or SNF5 increased the recruitment of HMTase G9a to the type 1 deiodinase (D1) promoter even with T3. Knocking-down either CARM1 or SNF5 also inhibited the down-regulation of histone macroH2A, which is correlated with transcriptional activation. Finally, knocking down CARM1 and SNF5 by siRNA impaired the association of these coactivators to the D1 promoter, suggesting functional importance of CARM1- SNF5 complex in T3-dependent transcriptional activation.