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Publication : Role for rearranged variable gene segments in directing secondary T cell receptor alpha recombination.

First Author  Hawwari A Year  2007
Journal  Proc Natl Acad Sci U S A Volume  104
Issue  3 Pages  903-7
PubMed ID  17210914 Mgi Jnum  J:119067
Mgi Id  MGI:3701139 Doi  10.1073/pnas.0608248104
Citation  Hawwari A, et al. (2007) Role for rearranged variable gene segments in directing secondary T cell receptor alpha recombination. Proc Natl Acad Sci U S A 104(3):903-7
abstractText  During the recombination of variable (V) and joining (J) gene segments at the T cell receptor alpha locus, a ValphaJalpha joint resulting from primary rearrangement can be replaced by subsequent rounds of secondary rearrangement that use progressively more 5' Valpha segments and progressively more 3' Jalpha segments. To understand the mechanisms that target secondary T cell receptor alpha recombination, we studied the behavior of a T cell receptor alpha allele (HYalpha) engineered to mimic a natural primary rearrangement of TRAV17 to Jalpha57. The introduced ValphaJalpha segment was shown to provide chromatin accessibility to Jalpha segments situated within several kilobases downstream and to suppress germ-line Jalpha promoter activity and accessibility at greater distances. As a consequence, the ValphaJalpha segment directed secondary recombination events to a subset of Jalpha segments immediately downstream from the primary rearrangement. The data provide the mechanistic basis for a model of primary and secondary T cell receptor alpha recombination in which recombination events progress in multiple small steps down the Jalpha array.
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