title: Activation of 12/23-RSS-dependent RAG cleavage by hSWI/SNF complex in the absence of transcription.
abstract: Maintenance of genomic integrity during antigen receptor gene rearrangements requires (1) regulated access of the V(D)J recombinase to specific loci and (2) generation of double-strand DNA breaks only after recognition of a pair of matched recombination signal sequences (RSSs). Here we recapitulate both key aspects of regulated recombinase accessibility in a cell-free system using plasmid substrates assembled into chromatin. We show that recruitment of the SWI/SNF chromatin-remodeling complex to both RSSs increases coupled cleavage by RAG1 and RAG2 proteins. SWI/SNF functions by altering local chromatin structure in the absence of RNA polymerase II-dependent transcription or histone modifications. These observations demonstrate a direct role for cis-sequence-regulated local chromatin remodeling in RAG1/2-dependent initiation of V(D)J recombination.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Hansen
authors.initials: H
authors.lastname: Du
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Ishii
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pazin
authors.forename: Ranjan
authors.initials: R
authors.lastname: Sen
mesh_terms: D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000502:physiology; D015321:Gene Rearrangement; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C070633:Gal-VP16; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; C499311:RAG2 protein, human; D011993:Recombinant Fusion Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D015534:Trans-Activators; D014157:Transcription Factors; C064658:RAG-1 protein
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