The Influence of Transcriptional Orientation on Endogenous Switch Region Function

Nat Immunol. 2003 May;4(5):435-41. doi: 10.1038/ni918.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Composition
  • Base Sequence
  • Chimera
  • DNA, Single-Stranded / chemistry
  • DNA, Single-Stranded / genetics
  • Immunoglobulin Switch Region*
  • Mice
  • Mice, Mutant Strains
  • Models, Genetic
  • Models, Immunological
  • Mutation
  • Transcription, Genetic

Substances

  • DNA, Single-Stranded