Histone acetylation and hSWI/SNF remodeling act in concert to stimulate V(D)J cleavage of nucleosomal DNA.
The ordered assembly of immunoglobulin and TCR genes by V(D)J recombination depends on the regulated accessibility of individual loci. We show here that the histone tails and intrinsic nucleosome structure pose significant impediments to V(D)J cleavage. However, alterations to nucleosome structure via histone acetylation or by stable hSWI/SNF-dependent remodeling greatly increase the accessibility of nucleosomal DNA to V(D)J cleavage. Moreover, acetylation and hSWI/SNF remodeling can act in concert on an individual nucleosome to achieve levels of V(D)J cleavage approaching those observed on naked DNA. These results are consistent with a model in which regulated recruitment of chromatin modifying activities is involved in mediating the lineage and stage-specific control of V(D)J recombination.
Kwon
J
J
Department of Molecular Biology Massachusetts General Hospital, Boston, MA 02114, USA.
Morshead
K B
KB
Guyon
J R
JR
Kingston
R E
RE
Oettinger
M A
MA
D000107:Acetylation; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D009687:Nuclear Proteins; D009707:Nucleosomes / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011995:Recombination, Genetic / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; C499311:RAG2 protein, human; C499336:SMARCA1 protein, human; C084011:SMARCA2 protein, human; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004247:DNA; C084108:SMARCA4 protein, human; D004265:DNA Helicases