TFII-I down-regulates a subset of estrogen-responsive genes through its interaction with an initiator element and estrogen receptor α
TFII-I down-regulates a subset of estrogen-responsive genes through its interaction with an initiator element and estrogen receptor α
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DOI：
10.1111/j.1365-2443.2006.00952.x
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发表时间：
2006-04-01
期刊：
影响因子：
2.1
通讯作者：
Handa, H
中科院分区：
文献类型：
--
作者：
Ogura, Y;Azuma, M;Handa, H
TFII-I 最初被鉴定为在体外与起始（Inr）元件结合的通用转录因子。随后的研究表明，TFII-I通过Inr元件或体内其他上游元件激活各种基因的转录。然而，由于迄今为止大多数关于 TFII-I 的研究仅限于过表达和报告基因测定，因此我们通过使用 siRNA 稳定敲低并检查内源基因的表达来重新评估 TFII-I 在体内的作用。与广泛接受的观点相反，我们在此表明 TFII-I 对于一般细胞活力并不重要，而是抑制 MCF-7 人乳腺癌细胞的生长。已知 MCF-7 细胞以雌激素依赖性方式增殖。通过分析 TFII-I 的细胞类型特异性生长抑制作用，我们发现证据表明 TFII-I 通过将雌激素受体 (ER) α 和辅阻遏物募集到这些启动子上，下调雌激素反应基因的子集，仅那些含有 Inr 元件的基因。因此，这项研究揭示了 TFII-I 作为转录和细胞增殖的负调节因子的意想不到的新作用。
TFII-I was initially identified as the general transcription factor that binds to initiator (Inr) elements in vitro. Subsequent studies have shown that TFII-I activates transcription of various genes either through Inr elements or through other upstream elements in vivo. Since, however, most studies so far on TFII-I have been limited to over-expression and reporter gene assays, we reevaluated the role of TFII-I in vivo by using stable knockdown with siRNA and by examining the expression of endogenous genes. Contrary to the widely accepted view, here we show that TFII-I is not important for cell viability in general but rather inhibits the growth of MCF-7 human breast cancer cells. MCF-7 cells are known to proliferate in an estrogen-dependent manner. Through analysis of TFII-I's cell-type specific growth inhibitory effect, we show evidence that TFII-I down-regulates a subset of estrogen-responsive genes, only those containing Inr elements, by recruiting estrogen receptor (ER) alpha and corepressors to these promoters. Thus, this study has revealed an unexpected new role of TFII-I as a negative regulator of transcription and cell proliferation.