INTERFERON-INDUCED NUCLEAR FACTORS THAT BIND A SHARED PROMOTER ELEMENT CORRELATE WITH POSITIVE AND NEGATIVE TRANSCRIPTIONAL CONTROL

INTERFERON-INDUCED NUCLEAR FACTORS THAT BIND A SHARED PROMOTER ELEMENT CORRELATE WITH POSITIVE AND NEGATIVE TRANSCRIPTIONAL CONTROL
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DOI:
10.1101/gad.2.4.383
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发表时间:
1988-04-01
影响因子:
10.5
通讯作者:
DARNELL, JE
DARNELL, JE
中科院分区:
生物学1区
文献类型:
--
作者:
LEVY, DE;KESSLER, DS;DARNELL, JE

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人类α-和β-干扰素(IFN)刺激一组先前静止基因的转录快速但短暂的增加。初始刺激不需要蛋白质合成,但由于需要合成新蛋白质的过程,反应持续时间被限制在几个小时。通过缺失分析和点突变,在诱导基因的 5'' 处鉴定出 IFN 刺激反应元件 (ISRE),并与其他启动子进行序列比较,确定共有元件 YAGTTTC(A/T)YTTTYCC。发现了两类与 ISRE 结合的 IFN 诱导核因子。最快速诱导的因子出现时没有新的蛋白质合成,而第二个因子需要活性蛋白质合成才能出现和维持。这些结合活性的出现和丧失的动力学与 IFN 刺激基因的激活和抑制相关。这些不同的IFN激活或诱导因子可以依次结合到相同的必需启动子元件上,首先增加转录,然后抑制转录。
Human .alpha.- and .beta.-interferons (IFNs) stimulate rapid but transient increases in transcription from a set of previously quiescent genes. Protein synthesis is not required for initial stimulation, but duration of the response is limited to a few hours by a process required synthesis of new proteins. An IFN-stimulated response element (ISRE) was identified 5'' to an inducible gene by deletion analysis and point mutagenesis, and sequence comparisons with other promoters defined the consensus element YAGTTTC(A/T)YTTTYCC. Two classes of IFN-inducible nuclear factors were found that bind to the ISRE. The most rapidly induced factor appeared without new protein synthesis, whereas a second factor required active protein synthesis for its appearance and maintenanc. The kinetics of appearance and loss of these binding activities correlate with the activation and repression of IFN-stimulated genes. These different IFN-activated or induced factors may bind sequentially to the same essential promoter element to first increase and then repress transcription.