Guermah Mohamed, Ge Kai, Chiang Cheng Ming, Roeder Robert G
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, 10021, New York, NY, USA
Mol Cell. 2003 Oct;12(4):991-1001. doi: 10.1016/s1097-2765(03)00396-4.
Human TFIID contains the TATA-binding protein (TBP) and several TBP-associated factors (hTAFs) that have been shown to play important roles, within TFIID, both in core promoter recognition and as coactivators. Here we show that the human TAF(II)43 (TAF8) is an integral component of a functional TFIID and an apparent ortholog to the recently reported mouse TBN, which is essential for early embryonic mouse developmental events. Significantly, we also show that TAF8 is dramatically induced and sequestered within TFIID upon differentiation of 3T3-L1 preadipocytes to adipocytes, whereas the expression of all other TAFs tested is slightly reduced. Moreover, when ectopically expressed, the histone fold domain of TAF8 acts as a dominant-negative mutant and selectively inhibits 3T3-L1 adipogenic differentiation. Furthermore TAF8 acts as a positive regulator of adipogenesis and reverses the inhibitory effect of its histone fold. These data suggest a selective role for TAF8 in a specific cell differentiation process(es).
人TFIID包含TATA结合蛋白(TBP)和几种TBP相关因子(hTAFs),这些因子已被证明在TFIID中,在核心启动子识别以及作为共激活因子方面都发挥着重要作用。在此我们表明,人TAF(II)43(TAF8)是功能性TFIID的一个组成部分,并且明显是最近报道的对小鼠早期胚胎发育事件至关重要的小鼠TBN的直系同源物。重要的是,我们还表明,在3T3-L1前脂肪细胞向脂肪细胞分化时,TAF8在TFIID内被显著诱导并隔离,而所有其他测试的TAFs的表达略有降低。此外,当异位表达时,TAF8的组蛋白折叠结构域作为显性负突变体起作用,并选择性地抑制3T3-L1脂肪生成分化。此外,TAF8作为脂肪生成的正调节因子,可逆转其组蛋白折叠的抑制作用。这些数据表明TAF8在特定细胞分化过程中具有选择性作用。