Differential DNA binding and transcription modulation by three T-box proteins, T, TBX1 and TBX2
Differential DNA binding and transcription modulation by three T-box proteins, T, TBX1 and TBX2
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DOI：
10.1016/s0378-1119(00)00417-0
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发表时间：
2000-11-27
期刊：
影响因子：
3.5
通讯作者：
Campbell, CE
中科院分区：
文献类型：
--
作者：
Sinha, S;Abraham, S;Campbell, CE
T-box 基因编码一系列系统发育上保守的 DNA 结合蛋白，可在胚胎发生过程中调节基因表达。虽然许多 T-box 基因的发育重要性已得到充分证明，但人们对家族成员在 DNA 结合特性和调节转录能力方面有何不同知之甚少。在这里，我们表明，尽管 TBX1、TBX2 和非洲爪蟾 T 蛋白 (Xbra) 在其 DNA 结合域中仅具有 50-60% 的同一性，但它们可以在体外结合相同的 DNA 序列。然而，这些蛋白质在三个重要方面有所不同。 TBX1 蛋白以二聚体形式结合回文 T 寡核苷酸，正如之前针对 Xbra 的报道，而 TBX2 似乎以单体形式结合相同的 DNA 序列。此外，T 蛋白/DNA 复合物在体外通过添加特异性抗体来稳定，而 TBX2/DNA 复合物则不能通过抗体来稳定。最重要的是，TBX2 抑制同一个嵌合报告质粒的转录，而 Xbra 激活转录。 TBX1虽然能够结合嵌合启动子，但对转录没有影响。因此，虽然 T-box 蛋白的 DNA 结合域具有显着的同源性，但这些蛋白在 DNA 结合和转录调节特性方面有所不同。这些结果表明，各种 T-box 蛋白虽然高度保守，但可能使用不同的机制来调节转录，并且可能在体内具有不同的靶标。 (C) 2000 Elsevier Science B.V. 保留所有权利。
T-box genes encode a family of phylogenetically conserved DNA-binding proteins that regulate gene expression during embryogenesis. While the developmental importance of many T-box genes has been well documented, little is known about how family members differ in their DNA binding properties and ability to modulate transcription. Here we show that although TBX1, TBX2 and the Xenopus T protein (Xbra) share only 50-60% identity within their DNA-binding domains they can bind the same DNA sequence in vitro. However, the proteins differ in three important respects. While TBX1 protein binds a palindromic T oligonucleotide as a dimer, as had been previously reported for Xbra, TBX2 appears to bind the same DNA sequence as a monomer. Also, T protein/DNA complexes are stabilized in vitro by the addition of specific antibodies, whereas TBX2/DNA complexes are not stabilized by antibodies. Most importantly, TBX2 represses while Xbra activates transcription of the same chimeric reporter plasmid. TBX1, although capable of binding to the chimeric promoter, has no effect on transcription. Thus, while the DNA binding domains of T-box proteins share substantial homology, these proteins differ in both their DNA binding and transcriptional modulation properties. These results suggest that the various T-box proteins, while highly conserved, likely use different mechanisms to modulate transcription and may have different targets in vivo. (C) 2000 Elsevier Science B.V. All rights reserved.