Regulation of TCRβ gene assembly by a promoter/enhancer holocomplex

Antigen receptor gene assembly is governed by transcriptional promoters and enhancers that communicate over large distances and modulate chromatin accessibility to V(D)J recombinase. The precise role of these cis-acting elements in opening chromatin at recombinase targets and the mechanisms underlying their crosstalk remain unclear. We show that the TCRP enhancer (E beta) directs long-range chromatin opening over both D beta J beta clusters. Strikingly, chromatin associated with the D beta 1 gene segment is refractory to Eo-mediated opening. Accessibility at D beta 1 is accompanied by the formation of a stable holocomplex between a Do-proximal promoter and E beta. These findings indicate a stepwise process for D beta -> J beta recombination that relies on distinct aspects of E beta activity: an intrinsic function that directs general chromatin opening and a cooperative function that facilitates the assembly of a promoter/enhancer holocomplex, unmasks the Doll gene segment, and triggers TCRP gene assembly.