Latinkić B V, Zeremski M, Lau L F
Department of Genetics, The University of Illinois College of Medicine, Chicago 60607-7170, USA.
Nucleic Acids Res. 1996 Apr 1;24(7):1345-51. doi: 10.1093/nar/24.7.1345.
The initial genomic response to serum growth factors is the transcriptional activation of a set of immediate-early genes. Serum-induced transcriptional activation of several of these genes involves the formation of a ternary complex that includes the serum response factor (SRF), a 62 kDa ternary complex factor (TCF) and a serum response element (SRE). TCF alone does not bind the SRE of the protooncogene c-fos, but requires the prior assembly of the SRF-SRE binary complex for it to be recruited into a ternary complex. Here we show that this SRF-SRE binary complex is not an obligatory prerequisite for the formation of a serum responsive ternary complex. We demonstrate that Elk-1, which has properties of TCF can recruit SRF into a ternary complex on elements that do not support formation of the SRF-DNA binary complex. We also show that for two immediate-early genes, pip92 and nur77, formation of the ternary complex may occur without the prior assembly of SRF-DNA binary complex. Finally, we show that the ability of different sequences to support formation of Elk-l-SRF-DNA ternary complex in vitro correlates with their ability to respond to serum growth factors in vivo. Our results suggest that a much broader range of DNA sequences than the consensus SRF and TCF binding sites can support ternary complex formation, and by inference, serum induction. Possible implications of these results are discussed.
对血清生长因子的初始基因组反应是一组立即早期基因的转录激活。血清诱导的这些基因中的几个基因的转录激活涉及三元复合物的形成，该复合物包括血清反应因子（SRF）、一种62 kDa的三元复合物因子（TCF）和一个血清反应元件（SRE）。单独的TCF不结合原癌基因c-fos的SRE，但需要SRF-SRE二元复合物预先组装才能被招募到三元复合物中。在这里，我们表明这种SRF-SRE二元复合物不是血清反应性三元复合物形成的必要先决条件。我们证明，具有TCF特性的Elk-1可以在不支持SRF-DNA二元复合物形成的元件上，将SRF招募到三元复合物中。我们还表明，对于两个立即早期基因pip92和nur77，三元复合物的形成可能在没有SRF-DNA二元复合物预先组装的情况下发生。最后，我们表明不同序列在体外支持Elk-1-SRF-DNA三元复合物形成的能力与其在体内对血清生长因子的反应能力相关。我们的结果表明，比SRF和TCF结合位点共有序列范围更广的DNA序列可以支持三元复合物的形成，并由此推断支持血清诱导。讨论了这些结果可能的意义。
