A conserved DNA structural control element modulates transcription of a mammalian gene.

A conserved DNA structural control element modulates transcription of a mammalian gene.
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保守的 DNA 结构控制元件调节哺乳动物基因的转录。

DOI:
10.1093/nar/20.24.6583
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发表时间:
1992
影响因子:
14.9
通讯作者:
Azizkhan,JC
Azizkhan,JC
中科院分区:
生物学2区
文献类型:
--
作者:
Pierce,AJ;Jambou,RC;Jensen,DE;Azizkhan,JC

文献摘要

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哺乳动物二氢叶酸还原酶(DHFR)基因启动子包含几个与蛋白质结合的保守序列元件,但也有其他保守的DNA序列没有足迹。我们在这里报道,这些保守的非足迹区域之一的突变增加了该启动子在体外和体内的转录。我们发现,这个保守区两侧有对甲基丙基-EDTA-Fe(II)超敏感的切割位点。此外,由该区域组成的双链寡核苷酸的多聚体在聚丙烯酰胺中的迁移速度比对照DNA快。移动性的差异不是弯曲的结果,初级序列也不包含预测移动性改变的特征。我们认为这个‘结构控制元件’是刚性的,通过抑制与该区域相邻的结合蛋白之间的相互作用来下调转录。
The mammalian dihydrofolate reductase (DHFR) gene promoters contain several conserved sequence elements which bind protein, and yet there are other conserved DNA sequences that do not footprint. We report here that mutation of one of these conserved non-footprinting regions increases transcription from this promoter bothin vitroandin vivo. We show that this conserved region is flanked by sites hypersensitive to cleavage by methidiumpropyl-EDTA-Fe(II). Furthermore, multimers of a double-stranded oligonucleotide comprised of this region display faster migration through polyacrylamide than control DNA. The difterence in mobility is not the result of bending, nor does the primary sequence contain features that would predict altered mobility. We propose that this ‘Structural Control Element’ is rigid and down-regulates transcription by inhibiting interactions between proteins binding adjacent to this region.