Defect in rearrangement of the most 5' TCR-J alpha following targeted deletion of T early alpha (TEA): implications for TCR alpha locus accessibility.
To address the role of the TEA germline transcription, which initiates upstream of the TCR-J alpha S, in the regulation of TCR-J alpha locus accessibility, we created a mouse in which this region has been removed by homologous recombination. Normal development of T alpha beta cells and the expression of other TCR alpha germline transcripts in TEA-/- mice ruled out an exclusive role for TEA in the overall accessibility of the J alpha cluster. However, the rearrangement of the most 5' J alpha (J alpha 61 to J alpha 53) was severely impaired, indicating that TEA may control the DNA accessibility of a particular J alpha window. Moreover, the relative usage of every J alpha segment was affected. These results are consistent with TEA acting as a "rearrangement-focusing" element, targeting the primary waves of V alpha-J alpha recombination to the most 5' J alpha S in an ongoing TCR-J alpha rearrangement model.
Villey
I
I
Développement Normal et Pathologique du Système Immunitaire, INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
Caillol
D
D
Selz
F
F
Ferrier
P
P
de Villartay
J P
JP
D000818:Animals; D004247:DNA / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic
D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA