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- W4234855744 abstract "Somatic hypermutation induced by activation-induced deaminase (AID) occurs at high densities between the Ig V gene promoter and intronic enhancer, which encompasses DNA encoding the rearranged V gene exon and J intron. It has been proposed that proximity between the promoter and enhancer defines the boundaries of mutation in V regions. However, depending on the J gene used, the distance between the promoter and enhancer is quite variable and may result in differential targeting around the V gene. To examine the effect of distance in mutation accumulation, we sequenced 320 clones containing different endogenous rearranged V genes in the IgH and Igκ loci from Peyer’s patch B cells of mice. Clones were grouped by their use of different J genes. Distances between the V gene and enhancer ranged from ∼2.3 kb of intron DNA for rearrangements using J1, ∼2.0 kb for rearrangements using J2, ∼1.6 kb for rearrangements using J3 (H) or 4 (κ), and 1.1 kb for rearrangements using J4 (H) or 5 (κ). Strikingly, >90% of intron mutations occurred within 1 kb downstream of the J gene for both H and κ clones, regardless of which J gene was used. Thus, there is no evidence that the intron sequence or enhancer plays a role in determining the extent of mutation. The results indicate that V region intron mutations are targeted by their proximity to the promoter, suggesting they result from AID interactions with RNA polymerase II over a 1-kb region." @default.
- W4234855744 created "2022-05-12" @default.
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- W4234855744 date "1994-06-11" @default.
- W4234855744 modified "2023-09-26" @default.
- W4234855744 title "Rabelais remembered" @default.
- W4234855744 doi "https://doi.org/10.1136/bmj.308.6943.1576" @default.
- W4234855744 hasPublicationYear "1994" @default.
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