Nature Immunology5, 1275 - 1281 (2004)
Published online: 7 November 2004; | doi:10.1038/ni1137
An evolutionarily conserved target motif for immunoglobulin class-switch recombination
Ali A Zarrin1, 3, Frederick W Alt1, Jayanta Chaudhuri1, Nicole Stokes1, Dhruv Kaushal1, Louis Du Pasquier2
& Ming Tian1, 3
1
Howard Hughes Medical Institute, The Children's Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard University Medical School, Boston, Massachusetts 02115, USA.
2
Institute of Zoology, University of Basel, Basel, Switzerland.
Immunoglobulin H class-switch recombination (CSR) occurs between switch regions and requires transcription and activation-induced cytidine deaminase (AID). Transcription through mammalian switch regions, because of their GC-rich composition, generates stable R-loops, which provide single-stranded DNA substrates for AID. However, we show here that the Xenopus laevis switch region S, which is rich in AT and not prone to form R-loops, can functionally replace a mouse switch region to mediate CSR in vivo. X. laevis S−mediated CSR occurred mostly in a region of AGCT repeats targeted by the AID−replication protein A complex when transcribed in vitro. We propose that AGCT is a primordial CSR motif that targets AID through a non-R-loop mechanism involving an AID−replication protein A complex.
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, which is rich in AT and not prone to form R-loops, can functionally replace a mouse switch region to mediate CSR in vivo. X. laevis S
