OCCUPATION OF THE C-FOS SERUM RESPONSE ELEMENT INVIVO BY A MULTI-PROTEIN COMPLEX IS UNALTERED BY GROWTH-FACTOR INDUCTION
OCCUPATION OF THE C-FOS SERUM RESPONSE ELEMENT INVIVO BY A MULTI-PROTEIN COMPLEX IS UNALTERED BY GROWTH-FACTOR INDUCTION
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DOI：
10.1038/340068a0
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发表时间：
1989-07-06
期刊：
影响因子：
64.8
通讯作者：
NORDHEIM, A
中科院分区：
文献类型：
--
作者：
HERRERA, RE;SHAW, PE;NORDHEIM, A
细胞外信号对人c-fosproto-致癌基因的快速瞬时诱导需要血清反应元件（SRE）1，2的存在。在体外与SRE结合的两种蛋白因子是血清反应因子（p67 SRF）3- 5和多肽p62（参考文献6）。这些多肽必须彼此相互作用，并与SRE相互作用，以有效地血清诱导c-fosgene 6。在这里，我们使用硫酸二甲酯基因组足迹7来建立SRE和侧翼序列上的体内蛋白质接触。在人A431细胞中，我们发现的保护和高反应性模式与p67 SRF、p62和至少一种紧邻p67 SRF 3'的其他蛋白的存在一致。我们在SRE内观察到的蛋白质-DNA接触在表皮生长因子诱导之前存在，并且在基因激活和随后的抑制期间不变。我们的研究结果表明，一个特定的DNA-蛋白质结构可以保持在c-fosSRE，无论基因的转录状态的变化。这种建立的结构通常在对细胞外信号的快速转录反应中是重要的。
RAPID, transient induction of the human c-fosproto-oncogene by extracellular signals requires the presence in els of the serum response element (SRE)1,2. Two protein factors that bind to the SREin vitroare the serum response factor (p67SRF)3—5and polypeptide p62 (ref. 6). These polypeptides must interact with one another and the SRE for efficient serum induction of the c-fosgene6. Here we use dimethyl sulphate genomic footprinting7to establish thein vivoprotein contacts on the SRE and flanking sequences. In human A431 cells the patterns of protection and hyper-reactivity that we find are consistent with the presence of p67SRF, p62, and at least one other protein immediately 3' to p67SRF. The protein-DNA contacts we observe within the SRE are present before induction by epidermal growth factor and are unchanged during gene activation and subsequent repression. Our results indicate that a specific DNA—protein architecture may be maintained at the c-fosSRE, regardless of changes in the transcriptional state of the gene. Such established structures could be important generally in rapid transcriptional responses to extracellular signals.