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Sequence-specific recognition of DNA in the nucleosome by pyrrole-imidazole polyamides

Gottesfeld, Joel M. and Melander, Christian and Suto, Robert K. and Raviol, Holger and Luger, Karolin and Dervan, Peter B. (2001) Sequence-specific recognition of DNA in the nucleosome by pyrrole-imidazole polyamides. Journal of Molecular Biology, 309 (3). pp. 615-629. ISSN 0022-2836. https://resolver.caltech.edu/CaltechAUTHORS:20160510-082728677

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1006/jmbi.2001.4694DOIArticle
http://www.sciencedirect.com/science/article/pii/S0022283601946947PublisherArticle
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2001 Academic Press. Received 7 February 2001; received in revised form 9 April 2001; accepted 9 April 2001. This work was supported by grants from the National Institutes of Health (GM57148 to J.M.G. and P.B.D. and GM61909 to K.L.). C.M. was supported by an NIH postdoctoral fellowship (GM19789) and R.K.S. was supported by the Basil O'Conner Starter Scholar award to K. L. We thank J. Ehley and S. Ebbesen for technical assistance.
Funders:
Funding AgencyGrant Number
NIHGM-57148
NIHGM-61909
NIH Postdoctoral FellowshipGM19789-02
March of Dimes FoundationUNSPECIFIED
Subject Keywords:nucleosome; core particle; pyrrole-imidazole polyamide
Issue or Number:3
Record Number:CaltechAUTHORS:20160510-082728677
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-082728677
Official Citation:Joel M. Gottesfeld, Christian Melander, Robert K. Suto, Holger Raviol, Karolin Luger, Peter B. Dervan, Sequence-specific Recognition of DNA in the Nucleosome by Pyrrole-Imidazole Polyamides, Journal of Molecular Biology, Volume 309, Issue 3, 8 June 2001, Pages 615-629, ISSN 0022-2836, http://dx.doi.org/10.1006/jmbi.2001.4694. (http://www.sciencedirect.com/science/article/pii/S0022283601946947)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66825
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:18 May 2016 18:51
Last Modified:26 Nov 2019 11:15

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