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Cell Rep. 2014 Jul 24;8(2):557-69. doi: 10.1016/j.celrep.2014.06.021. Epub 2014 Jul 10.

The strength of an Ig switch region is determined by its ability to drive R loop formation and its number of WGCW sites.

Author information

1
USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Molecular and Computational Biology Section, Department of Biological Sciences, USC Dornsife, University of Southern California, Los Angeles, CA 90033, USA; Departments of Pathology, Biochemistry & Molecular Biology, Molecular Microbiology & Immunology, and Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
2
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
3
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Electronic address: yuke@msu.edu.
4
USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Molecular and Computational Biology Section, Department of Biological Sciences, USC Dornsife, University of Southern California, Los Angeles, CA 90033, USA; Departments of Pathology, Biochemistry & Molecular Biology, Molecular Microbiology & Immunology, and Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: lieber@usc.edu.

Abstract

R loops exist at the murine IgH switch regions and possibly other locations, but their functional importance is unclear. In biochemical systems, R loop initiation requires DNA sequence regions containing clusters of G nucleotides, but cellular studies have not been done. Here, we vary the G-clustering, total switch region length, and the number of target sites (WGCW sites for the activation-induced deaminase) at synthetic switch regions in a murine B cell line to determine the effect on class switch recombination (CSR). G-clusters increase CSR regardless of their immediate proximity to the WGCW sites. This increase is accompanied by an increase in R loop formation. CSR efficiency correlates better with the absolute number of WGCW sites in the switch region rather than the total switch region length or density of WGCW sites. Thus, the overall strength of the switch region depends on G-clusters, which initiate R loop formation, and on the number of WGCW sites.

PMID:
25017067
PMCID:
PMC4118936
DOI:
10.1016/j.celrep.2014.06.021
[Indexed for MEDLINE]
Free PMC Article

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