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Molecular recognition of the nucleosomal "supergroove"

Edayathumangalam, Rajeswari S. and Weyermann, Philipp and Gottesfeld, Joel M. and Dervan, Peter B. and Luger, Karolin (2004) Molecular recognition of the nucleosomal "supergroove". Proceedings of the National Academy of Sciences of the United States of America, 101 (18). pp. 6864-6869. ISSN 0027-8424. PMCID PMC406433.

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Chromatin is the physiological substrate in all processes involving eukaryotic DNA. By organizing 147 base pairs of DNA into two tight superhelical coils, the nucleosome generates an architecture where DNA regions that are 80 base pairs apart on linear DNA are brought into close proximity, resulting in the formation of DNA "supergrooves." Here, we report the design of a hairpin polyamide dinner that targets one such supergroove. The 2-Angstrom crystal structure of the nucleosome-polyamide complex shows that the bivalent "clamp" effectively crosslinks the two gyres of the DNA superhelix, improves positioning of the DNA on the histone octamer, and stabilizes the nucleosome against dissociation. Our findings identify nucleosomal supergrooves as platforms for molecular recognition of condensed eukaryotic DNA. In vivo, supergrooves may foster synergistic protein-protein interactions by bringing two regulatory elements into juxtaposition. Because supergroove formation is independent of the translational position of the DNA on the histone octamer, accurate nucleosome positioning over regulatory elements is not required for supergroove participation in eukaryotic gene regulation.

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Additional Information:© 2004 by the National Academy of Sciences. From the cover. Contributed by Peter B. Dervan, March 16, 2004. Published online before print April 20, 2004, 10.1073/pnas.0401743101 We thank Gerry McDermott and Keith Henderson at the Advanced Light Source (Berkeley, CA) for help with data collection; Stephanie Ebbesen and Pamela Dyer for help with reagents; and Laurie Stargell and Clara Kielkopf for helpful comments. This work was supported by a grant supplement from the National Institutes of Health (to K.L., J.M.G., and P.B.D.) and by a postdoctoral fellowship from the Swiss National Science Foundation (to P.W.). Data deposition: The atomic coordinates and structure factors for NCP146–PW12 have been deposited in the Protein Data Bank, (PDB ID code 1S32).
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Swiss National Science Foundation (SNSF)UNSPECIFIED
PubMed Central ID:PMC406433
Record Number:CaltechAUTHORS:EDApnas04
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Official Citation:Rajeswari S. Edayathumangalam, Philipp Weyermann, Joel M. Gottesfeld, Peter B. Dervan, and Karolin Luger Molecular recognition of the nucleosomal “supergroove” PNAS 2004 101 (18) 6864-6869; published ahead of print April 20, 2004, doi:10.1073/pnas.0401743101
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1369
Deposited By: Tony Diaz
Deposited On:12 Jan 2006
Last Modified:09 May 2016 20:54

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