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Publication : The influence of transcriptional orientation on endogenous switch region function.

First Author  Shinkura R Year  2003
Journal  Nat Immunol Volume  4
Issue  5 Pages  435-41
PubMed ID  12679811 Mgi Jnum  J:97050
Mgi Id  MGI:3574197 Doi  10.1038/ni918
Citation  Shinkura R, et al. (2003) The influence of transcriptional orientation on endogenous switch region function. Nat Immunol 4(5):435-41
abstractText  Immunoglobulin heavy chain (IgH) class switch recombination (CSR) takes place between large switch (S) regions that precede exons of the constant region. The precise functions of the S region are controversial, although transcription of the S region targets CSR. We have tested the effects of deletion, inversion and replacement of the endogenous 12-kilobase S(gamma1) region on CSR in vivo. Here we show that S(gamma1) is required for CSR, that CSR is effected by a 1-kilobase sequence that generates a G-rich transcript, and that inversion of S(gamma1) or the G-rich sequence decreases CSR. We conclude that S(gamma1) function is dependent on orientation and lacks an absolute requirement for common S region motifs. We propose that single-stranded DNA stabilized by transcription-dependent, higher order structures is a primary substrate of CSR.
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