Activation of 12/23-RSS-dependent RAG cleavage by hSWI/SNF complex in the absence of transcription

作者：Du Hansen; Ishii Haruhiko; Pazin Michael J; Sen Ranjan^*

来源：Molecular Cell, 2008, 31(5): 641-649.

DOI：10.1016/j.molcel.2008.08.012

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.

• 出版日期2008-9-5