T cell receptor genes are created by stitching together three gene segments—V, D, and J—in different arrangements. But how each set of T cells selects its segments is not clear. Xiong et al. (page 929) now find that, for a set of fetal T cell 
chains, the appeal of a V segment lies in its location relative to the chosen J segment.
In the fetal stage, T cells prefer to use V3 or V4 gene segments, whereas T cells in the adult thymus instead use V2 or V5. Because V3 and V4 are closer to the J segments, Xiong et al. wondered whether V segment selection is dictated simply by their position. Closer V segments are used preferentially in fetal immunoglobulin genes as well, but in that case, proximity correlated with greater transcription and histone acetylation.
To test their new idea, the group engineered mice in which the locus was altered to replace the V3 segment with a V2 segment. The fetal T cells in these mice now included the new V2 segment in preference to the more distant V2 segment. They only included more distant gene segments if closer segments were deleted. How the nearby segments shut out their more remote neighbors is not yet known.
The accessibility of the V segments seemed to be equal across the board in fetal cells, as Xiong et al. found that transcription rates didn't predict which segments were used. But in adult T cells, the unused segments had lower levels of transcription. Perhaps the gene segments used during the fetal stage become inaccessible during adulthood, leaving only more distant choices. 
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
