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Chromatin remodeling directly activates V(D)J recombination

Cherry, Sara R. and Baltimore, David (1999) Chromatin remodeling directly activates V(D)J recombination. Proceedings of the National Academy of Sciences of the United States of America, 96 (19). pp. 10788-10793. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:CHEpnas99

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Abstract

V(D)J recombination substrate choice is regulated to ensure that the appropriate gene segments are rearranged during lymphocyte development. It has been proposed that regulation of substrate usage is determined by changes in accessibility of the DNA targets. We show that Rag-mediated recombination of an episomal substrate in cells is affected by its packaging into chromatin. Chromatinized substrates were inefficiently rearranged, and methylation further reduced recombination. Disruption of nucleosomes by using butyrate on methylated substrates was sufficient to activate recombination, and dexamethasone could activate recombination in the absence of detectable transcription. Therefore, chromatin structure, and its manipulation by altering nucleosome positioning, can directly affect recombination efficiencies.


Item Type:Article
Additional Information:© 1999 by The National Academy of Sciences. Contributed by David Baltimore, July 15, 1999. We thank T. Baker, S. Bell, and C. Roman for advice and critical reading of the manuscript. We thank T. Archer for chromatin protocols. We are grateful to K. Alexandropoulos, B. Chen, K. Collins, J. Jacob, T. Koleske, M. Porteus, I. Stancovski, and other members of the Baltimore Lab for advice and discussions. This work was supported by a National Institutes of Health grant.
Subject Keywords:TUMOR VIRUS PROMOTER, EPSTEIN-BARR VIRUS, TRANSCRIPTIONAL ADAPTER, IMMUNOGLOBULIN GENES, THYROID-HORMONE, JOINING SIGNALS, MMTV PROMOTER, CELL-CYCLE, IN-VIVO, RECEPTOR
Record Number:CaltechAUTHORS:CHEpnas99
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:CHEpnas99
Alternative URL:http://www.pnas.org/cgi/content/abstract/96/19/10788
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:574
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:25 Aug 2005
Last Modified:14 Nov 2014 19:18

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