The TBN protein, which is essential for early embryonic mouse development, is an inducible TAFII implicated in adipogenesis

The TBN protein, which is essential for early embryonic mouse development, is an inducible TAFII implicated in adipogenesis
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DOI:
10.1016/s1097-2765(03)00396-4
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发表时间:
2003-10-01
期刊:
影响因子:
16
通讯作者:
Roeder, RG
Roeder, RG
中科院分区:
生物学1区
文献类型:
--
作者:
Guermah, M;Ge, K;Roeder, RG

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人类TFIID包含tata结合蛋白(TBP)和几个TBP相关因子(hTAFs),这些因子已被证明在TFIID中发挥重要作用,无论是在核心启动子识别还是作为共激活因子。在这里,我们发现人类TAF(II)43 (TAF8)是功能性TFIID的一个组成部分,并且与最近报道的小鼠TBN明显同源,这对小鼠早期胚胎发育事件至关重要。值得注意的是,我们还发现,当3T3-L1前脂肪细胞向脂肪细胞分化时,TAF8在TFIID中被显著诱导和隔离,而所有其他TAFs的表达都略有降低。此外,当异位表达时,TAF8的组蛋白折叠结构域作为显性阴性突变体,选择性地抑制3T3-L1成脂分化。此外,TAF8作为脂肪形成的积极调节因子,并逆转其组蛋白折叠的抑制作用。这些数据表明TAF8在特定的细胞分化过程中具有选择性作用。
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).