Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 321, Issue 2, Pages 249-263Publisher
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/S0022-2836(02)00598-3
Keywords
nucleosome; transcription; pyrrole-imidazole polyamide
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Funding
- NIGMS NIH HHS [R01 GM061909, GM61909, GM57148, GM19789] Funding Source: Medline
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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.
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