title: Regulation of TCRbeta gene assembly by a promoter/enhancer holocomplex.
abstract: 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 TCRbeta enhancer (Ebeta) directs long-range chromatin opening over both DbetaJbeta clusters. Strikingly, chromatin associated with the Dbeta1 gene segment is refractory to Ebeta-mediated opening. Accessibility at Dbeta1 is accompanied by the formation of a stable holocomplex between a Dbeta-proximal promoter and Ebeta. These findings indicate a stepwise process for Dbeta --> Jbeta recombination that relies on distinct aspects of Ebeta activity: an intrinsic function that directs general chromatin opening and a cooperative function that facilitates the assembly of a promoter/enhancer holocomplex, unmasks the Dbeta1 gene segment, and triggers TCRbeta gene assembly.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Oestreich
authors.forename: Robin Milley
authors.initials: RM
authors.lastname: Cobb
authors.forename: Steven
authors.initials: S
authors.lastname: Pierce
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Pierre
authors.initials: P
authors.lastname: Ferrier
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Oltz
mesh_terms: D000818:Animals; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics*; D019674:Genes, T-Cell Receptor beta; D051379:Mice; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic