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Mol Immunol
2015 Oct 01;672 Pt B:524-31. doi: 10.1016/j.molimm.2015.07.039.
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The repetitive portion of the Xenopus IgH Mu switch region mediates orientation-dependent class switch recombination.
Zhang ZZ
,
Pannunzio NR
,
Lu Z
,
Hsu E
,
Yu K
,
Lieber MR
.
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Vertebrates developed immunoglobulin heavy chain (IgH) class switch recombination (CSR) to express different IgH constant regions. Most double-strand breaks for Ig CSR occur within the repetitive portion of the switch regions located upstream of each set of constant domain exons for the Igγ, Igα or Igϵ heavy chain. Unlike mammalian switch regions, Xenopus switch regions do not have a high G-density on the non-template DNA strand. In previous studies, when Xenopus Sμ DNA was moved to the genome of mice, it is able to support substantial CSR when it is used to replace the murine Sγ1 region. Here, we tested both the 2kb repetitive portion and the 4.6 kb full-length portions of the Xenopus Sμ in both their natural (forward) orientation relative to the constant domain exons, as well as the opposite (reverse) orientation. Consistent with previous work, we find that the 4.6 kb full-length Sμ mediates similar levels of CSR in both the forward and reverse orientations. Whereas, the forward orientation of the 2kb portion can restore the majority of the CSR level of the 4.6 kb full-length Sμ, the reverse orientation poorly supports R-looping and no CSR. The forward orientation of the 2kb repetitive portion has more GG dinucleotides on the non-template strand than the reverse orientation. The correlation of R-loop formation with CSR efficiency, as demonstrated in the 2kb repetitive fragment of the Xenopus switch region, confirms a role played by R-looping in CSR that appears to be conserved through evolution.
Boguslawski,
Characterization of monoclonal antibody to DNA.RNA and its application to immunodetection of hybrids.
1986, Pubmed
Boguslawski,
Characterization of monoclonal antibody to DNA.RNA and its application to immunodetection of hybrids.
1986,
Pubmed
Bransteitter,
Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase.
2003,
Pubmed
Chaudhuri,
Class-switch recombination: interplay of transcription, DNA deamination and DNA repair.
2004,
Pubmed
Daniels,
RNA:DNA complex formation upon transcription of immunoglobulin switch regions: implications for the mechanism and regulation of class switch recombination.
1995,
Pubmed
Du Pasquier,
The immune system of Xenopus.
1989,
Pubmed
,
Xenbase
Du Pasquier,
B-cell development in the amphibian Xenopus.
2000,
Pubmed
,
Xenbase
Dunnick,
Germline transcription and switch recombination of a transgene containing the entire H chain constant region locus: effect of a mutation in a STAT6 binding site in the gamma 1 promoter.
2004,
Pubmed
Hackney,
DNA targets of AID evolutionary link between antibody somatic hypermutation and class switch recombination.
2009,
Pubmed
Hadji-Azimi,
Studies on Xenopus laevis immunoglobulins.
1971,
Pubmed
,
Xenbase
Han,
Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination.
2011,
Pubmed
Honjo,
Molecular mechanism of class switch recombination: linkage with somatic hypermutation.
2002,
Pubmed
Hsu,
A third immunoglobulin class in amphibians.
1985,
Pubmed
,
Xenbase
Huang,
Downstream boundary of chromosomal R-loops at murine switch regions: implications for the mechanism of class switch recombination.
2006,
Pubmed
Huang,
Sequence dependence of chromosomal R-loops at the immunoglobulin heavy-chain Smu class switch region.
2007,
Pubmed
Kinoshita,
A hallmark of active class switch recombination: transcripts directed by I promoters on looped-out circular DNAs.
2001,
Pubmed
Mashoof,
Ancient T-independence of mucosal IgX/A: gut microbiota unaffected by larval thymectomy in Xenopus laevis.
2013,
Pubmed
,
Xenbase
Mussmann,
Microsites for immunoglobulin switch recombination breakpoints from Xenopus to mammals.
1997,
Pubmed
,
Xenbase
Phillips,
The sub-nanomolar binding of DNA-RNA hybrids by the single-chain Fv fragment of antibody S9.6.
2013,
Pubmed
Roy,
Mechanism of R-loop formation at immunoglobulin class switch sequences.
2008,
Pubmed
Roy,
G clustering is important for the initiation of transcription-induced R-loops in vitro, whereas high G density without clustering is sufficient thereafter.
2009,
Pubmed
Roy,
Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site.
2010,
Pubmed
Shinkura,
The influence of transcriptional orientation on endogenous switch region function.
2003,
Pubmed
Stavnezer,
Evolution of isotype switching.
2004,
Pubmed
Yu,
R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells.
2003,
Pubmed
Yu,
Nucleic acid structures and enzymes in the immunoglobulin class switch recombination mechanism.
2003,
Pubmed
Zarrin,
An evolutionarily conserved target motif for immunoglobulin class-switch recombination.
2004,
Pubmed
,
Xenbase
Zhang,
The role of G-density in switch region repeats for immunoglobulin class switch recombination.
2014,
Pubmed
Zhang,
Complexities due to single-stranded RNA during antibody detection of genomic rna:dna hybrids.
2015,
Pubmed
Zhang,
The strength of an Ig switch region is determined by its ability to drive R loop formation and its number of WGCW sites.
2014,
Pubmed
Zhu,
Origin of immunoglobulin isotype switching.
2012,
Pubmed
