Details

Autor(en) / Beteiligte

• Zhang, Zheng Z.
• Pannunzio, Nicholas R.
• Lu, Zhengfei
• Hsu, Ellen
• Yu, Kefei
• Lieber, Michael R.

Titel

The repetitive portion of the Xenopus IgH Mu switch region mediates orientation-dependent class switch recombination

Ist Teil von

• Molecular immunology, 2015-10, Vol.67 (2), p.524-531

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• •Xenopus Sμ (XSμ) has a highly repetitive 2kb region rich in WGCW.•The 2kb XSμ forms R-loops when in the physiologic orientation in B cells.•The 2kb XSμ portion supports Ig CSR in B cells, but only in the forward orientation.•The relation between R-loop formation and Ig CSR may be conserved in evolution. 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 4.6kb 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 4.6kb 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 4.6kb 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.