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Molecular and Cellular Biology, April 2003, p. 2438-2450, Vol. 23, No. 7
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.7.2438-2450.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Changes in Histone Acetylation Are Associated with Differences in Accessibility of VH Gene Segments to V-DJ Recombination during B-Cell Ontogeny and Development

Kristen Johnson,1 Cristina Angelin-Duclos,1,{dagger} Sinae Park,1 and Kathryn L. Calame1,2*

Department of Microbiology,1 Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 100322

Received 5 August 2002/ Returned for modification 23 September 2002/ Accepted 19 December 2002

Although V(D)J recombination is thought to be regulated by changes in the accessibility of chromatin to the recombinase machinery, the mechanisms responsible for establishing "open" chromatin are poorly understood. We performed a detailed study of the acetylation status of histones associated with 11 VH gene segments, their flanking regions, and various intergenic elements during B-cell development and ontogeny, when V(D)J recombination is highly regulated. Histone H4 shows higher and more-regulated acetylation than does histone H3 in the VH locus. In adult pro-B cells, VH gene segments are acetylated prior to V(D)J rearrangement, with higher acetylation associated with JH-distal VH gene segments. While large regions of the VH locus have similar patterns of histone acetylation, acetylation is narrowly confined to the gene segments, their flanking promoters, and recombinase signal sequence elements. Thus, histone acetylation in the VH locus is both locally and globally regulated. Increased histone acetylation accompanies preferential recombination of JH-proximal VH gene segments in early B-cell ontogeny, and decreased histone acetylation accompanies inhibition of V-DJ recombination in a transgenic model of immunoglobulin heavy-chain allelic exclusion. Thus, changes in histone acetylation appear to be important for both promotion and inhibition of V-DJ rearrangement during B-cell ontogeny and development.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University College of Physicians and Surgeons, 701 W. 168th St., HHSC 1202, New York, NY 10032. Phone: (212) 305-3504. Fax: (212) 305-1468. E-mail: klc1{at}columbia.edu.

{dagger} Present address: Laboratoire de Biologie Moleculaire et Cellulaire, Ecole Normale Superieure de Lyon, France.

Molecular and Cellular Biology, April 2003, p. 2438-2450, Vol. 23, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.7.2438-2450.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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