Activation of V(D)J recombination at the IgH chain JH locus occurs within a 6-kilobase chromatin domain and is associated with nucleosomal remodeling

The Journal of Immunology : Official Journal of the American Association of Immunologists
J MaësM Goodhardt

Abstract

IgH genes are assembled during early B cell development by a series of regulated DNA recombination reactions in which DH and JH segments are first joined followed by V(H) to DJH rearrangement. Recent studies have highlighted the role of chromatin structure in the control of V(D)J recombination. In this study, we show that, in murine pro-B cell precursors, the JH segments are located within a 6-kb DNase I-sensitive chromatin domain containing acetylated histones H3 and H4, which is delimited 5' by the DQ52 promoter element and 3' by the intronic enhancer. Within this domain, the JH segments are covered by phased nucleosomes. High-resolution mapping of nucleosomes reveals that, in pro-B cells, unlike recombination refractory nonlymphoid cells, the recombination signal sequences flanking the four JH segments are located in regions of enhanced micrococcal nuclease and restriction enzyme accessibility, corresponding to either nucleosome-free regions or DNA rendered accessible within a nucleosome. These results support the idea that nucleosome remodeling provides an additional level of control in the regulation of Ig locus accessibility to recombination factors in B cell precursors.

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Citations

Jun 11, 2011·Nature Reviews. Immunology·Howard Cedar, Yehudit Bergman
Jan 10, 2012·Annual Review of Immunology·Claudia BossenCornelis Murre
May 21, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hrisavgi D Kondilis-MangumMichael S Krangel
Jun 8, 2013·Journal of Cellular Biochemistry·Marcela StuardoSoraya Gutierrez
Oct 15, 2008·Journal of Cellular Physiology·Marcela StuardoSoraya E Gutiérrez
Jul 18, 2008·Molecular BioSystems·Adam J Bowen, Anne E Corcoran
Sep 14, 2010·Seminars in Immunology·Yehudit Bergman, Howard Cedar
Sep 25, 2010·Seminars in Immunology·Ramesh Subrahmanyam, Ranjan Sen

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