期刊
NATURE IMMUNOLOGY
卷 4, 期 5, 页码 435-441出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni918
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- NIAID NIH HHS [AI07512, AI31541] Funding Source: Medline
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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