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Publication : Chromosomal position of a VH gene segment determines its activation and inactivation as a substrate for V(D)J recombination.

First Author  Bates JG Year  2007
Journal  J Exp Med Volume  204
Issue  13 Pages  3247-56
PubMed ID  18056289 Mgi Jnum  J:130421
Mgi Id  MGI:3771660 Doi  10.1084/jem.20071787
Citation  Bates JG, et al. (2007) Chromosomal position of a VH gene segment determines its activation and inactivation as a substrate for V(D)J recombination. J Exp Med 204(13):3247-56
abstractText  Complete IgHC gene rearrangement occurs only in B cells in a stage-specific and ordered manner. We used gene targeting to reposition a distal V(H) gene segment to a region just 5' of the D(H) gene cluster and found its activation to be highly dependent on the chromosomal domain within which it resides. The targeted V(H) gene segment rearranged at a higher frequency than its endogenous counterpart, its rearrangement was no longer ordered, and its ability to be silenced by allelic exclusion was lost. Additionally, the targeted V(H) gene segment lost lineage specificity, as VDJ(H) rearrangement was observed in thymocytes. These data suggest that locus contraction, mimicked by proximal targeting, can override any regulation imposed by DNA sequences immediately surrounding V(H) gene segments.
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