Regulation of  T Cell Receptor δ Gene Rearrangement by CBF/PEBP2

We have analyzed transgenic mice carrying versions of a human T cell receptor (TCR)-δ gene minilocus to study the developmental control of  VDJ (variable/diversity/joining) recombination. Previous data indicated that a 1.4-kb DNA fragment carrying the TCR-δ enhancer (Eδ) efficiently activates minilocus VDJ recombination in vivo. We tested whether the transcription factor CBF/PEBP2 plays an important role in the ability of Eδ to activate VDJ recombination by analyzing VDJ recombination in mice carrying a minilocus in which the δE3 element of Eδ includes a mutated CBF/PEBP2 binding site. The enhancer-dependent VD to J step of minilocus rearrangement was dramatically inhibited in three of four transgenic lines, arguing that the binding of CBF/PEBP2 plays a role in modulating local accessibility to the VDJ recombinase in vivo. Because mutation of the δE3 binding site for the transcription factor c-Myb had previously established a similar role for c-Myb, and because a 60-bp fragment of Eδ carrying δE3 and δE4 binding sites for CBF/PEBP2, c-Myb, and GATA-3 displays significant enhancer activity in transient transfection experiments, we tested whether this fragment of Eδ is sufficient to