ANALYSIS OF SP1 INVIVO REVEALS MULTIPLE TRANSCRIPTIONAL DOMAINS, INCLUDING A NOVEL GLUTAMINE-RICH ACTIVATION MOTIF

ANALYSIS OF SP1 INVIVO REVEALS MULTIPLE TRANSCRIPTIONAL DOMAINS, INCLUDING A NOVEL GLUTAMINE-RICH ACTIVATION MOTIF
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DOI:
10.1016/0092-8674(88)90144-4
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发表时间:
1988-12-02
期刊:
影响因子:
64.5
通讯作者:
TJIAN, R
TJIAN, R
中科院分区:
生物学1区
文献类型:
--
作者:
COUREY, AJ;TJIAN, R

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我们采用果蝇组织培养细胞作为研究哺乳动物转录因子结构和功能的宿主系统。这些细胞提供了一个Sp1缺陷的背景,并已被用于互补试验,以确定人类转录因子Sp1的功能结构域。SV40的早期启动子,其中包含6个Sp1结合位点(GC盒),诱导高达500倍,在果蝇细胞中的Sp1的表达,而较少的网站启动子激活效率较低。对Sp1突变体的分析揭示了DNA结合结构域之外负责介导转录激活的多个不同区域。两个最活跃的结构域,这似乎是功能上彼此冗余,由一个不寻常的结构,具有非常低的电荷密度,但惊人的高谷氨酰胺含量。一些其他的序列特异性转录因子,如果蝇zeste蛋白和几个同源结构域蛋白,含有谷氨酰胺丰富的延伸,我们建议,这些谷氨酰胺丰富的结构域代表了一种新的结构基序的转录激活。
We have adopted Drosophila tissue culture cells as a host system for studying the structure and function of mammalian transcription factors. These cells provide an Sp1-deficient background and have been used in a complementation assay to identify functional domains of human transcription factor Sp1. The SV40 early promoter, which contains six Sp1 binding sites (GC boxes), is induced up to 500-fold in Drosophila cells by the expression of Sp1, whereas promoters with fewer sites are activated less efficiently. Analysis of Sp1 mutants reveals multiple distinct regions outside of the DNA binding domain that are responsible for mediating transcriptional activation. The two most active domains, which appear to be functionally redundant with one another, consist of an unusual structure with a very low charge density, but a strikingly high glutamine content. A number of other sequence-specific transcription factors, such as the Drosophila zeste protein and several homeodomain proteins, contain glutamine-rich stretches, and we propose that these glutamine-rich domains represent a novel structural motif for transcriptional activation.