Blocking transcription through a nucleosome with synthetic DNA ligands
Blocking transcription through a nucleosome with synthetic DNA ligands
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DOI：
10.1016/s0022-2836(02)00598-3
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发表时间：
2002-08-09
影响因子：
5.6
通讯作者：
Luger, K
中科院分区：
文献类型：
--
作者：
Gottesfeld, JM;Belitsky, JM;Luger, K
吡咯-咪唑聚酰胺。是合成的配体，结合在DNA的小凹槽中。先前的研究已经确定，核小体DNA上远离组蛋白八聚体的位点，甚至部分面向组蛋白八聚体的位点，完全可以被Py-Im聚酰胺分子识别，并且核小体在配体结合时保持完全折叠。两种聚酰胺结合在海胆5s基因核小体定位序列内，抑制热诱导的核小体滑动和噬菌体T7 RNA聚合酶从核小体模板的转录，但不抑制无组蛋白DNA的转录。这些聚酰胺防止组蛋白八聚体被RNA聚合酶重新定位，从而抑制延长聚合酶通过核小体DNA。这些结果明确地确立了T7 RNA聚合酶转录核小体模板所需的八聚体流动性。(C) 2002 Elsevier Science Ltd.版权所有。
Pyrrole-imidazole (Py-Im) polyamides. are synthetic ligands that bind in the minor groove of DNA. Previous studies have established that sites on nucleosomal DNA facing away from the histone octamer, or even partially facing the histone octamer, are fully accessible for molecular recognition by Py-Im polyamides, and that nucleosomes remain fully folded upon ligand binding. Two polyamides that bind within the sea urchin 5 S gene nucleosome positioning sequence inhibit both heat-induced nucleosome sliding and transcription by bacteriophage T7 RNA polymerase from the nucleosomal template, but not from histone-free DNA. These polyamides prevent repositioning of the histone octamer by RNA polymerase, and thereby inhibit passage of the elongating polymerase through nucleosomal DNA. These results establish unambiguously the requirement for octamer mobility for transcription of nucleosomal templates by T7 RNA polymerase. (C) 2002 Elsevier Science Ltd. All rights reserved.