Sequence-specific Recognition of DNA in the Nucleosome by Pyrrole-Imidazole Polyamides

The ability of DNA-binding proteins to recognize their cognate sites in chromatin is restricted by the structure and dynamics of nucleosomal DNA, and by the translational and rotational positioning of the histone octamer. Here, we use six different pyrrole-imidazole polyamides as sequence-specific m...

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Bibliographic Details
Published in:Journal of molecular biology 2001-06, Vol.309 (3), p.615-629
Main Authors: Gottesfeld, Joel M., Melander, Christian, Suto, Robert K., Raviol, Holger, Luger, Karolin, Dervan, Peter B.
Format: Article
Language:English
Subjects:
Base Sequence
Binding Sites
core particle
Deoxyribonuclease I - metabolism
DNA - chemistry
DNA - genetics
DNA - metabolism
DNA Footprinting
DNA, Satellite - chemistry
DNA, Satellite - genetics
DNA, Satellite - metabolism
Histones - chemistry
Histones - metabolism
Hydroxyl Radical - metabolism
Imidazoles - chemistry
Imidazoles - metabolism
Models, Molecular
Molecular Probes - chemistry
Molecular Probes - metabolism
Molecular Sequence Data
Nucleic Acid Conformation
nucleosome
Nucleosomes - chemistry
Nucleosomes - genetics
Nucleosomes - metabolism
Nylons - chemistry
Nylons - metabolism
pyrrole-imidazole polyamide
pyrrole-imidazole polyamides
Pyrroles - chemistry
Pyrroles - metabolism
Substrate Specificity
Thermodynamics
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Summary:The ability of DNA-binding proteins to recognize their cognate sites in chromatin is restricted by the structure and dynamics of nucleosomal DNA, and by the translational and rotational positioning of the histone octamer. Here, we use six different pyrrole-imidazole polyamides as sequence-specific molecular probes for DNA accessibility in nucleosomes. We show that sites on nucleosomal DNA facing away from the histone octamer, or even partially facing the histone octamer, are fully accessible and that nucleosomes remain fully folded upon ligand binding. Polyamides only failed to bind where sites are completely blocked by interactions with the histone octamer. Removal of the amino-terminal tails of either histone H3 or histone H4 allowed these polyamides to bind. These results demonstrate that much of the DNA in the nucleosome is freely accessible for molecular recognition in the minor groove, and also support a role for the amino-terminal tails of H3 and H4 in modulating accessibility of nucleosomal DNA.
ISSN:0022-2836
1089-8638
DOI:10.1006/jmbi.2001.4694