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 underlyi...

Full description

Saved in:
Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2006-04, Vol.24 (4), p.381-391
Main Authors: Oestreich, Kenneth J., Cobb, Robin Milley, Pierce, Steven, Chen, Jianzhu, Ferrier, Pierre, Oltz, Eugene M.
Format: Article
Language:English
Subjects:
MOLIMMUNO
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 TCRβ enhancer (Eβ) directs long-range chromatin opening over both DβJβ clusters. Strikingly, chromatin associated with the Dβ1 gene segment is refractory to Eβ-mediated opening. Accessibility at Dβ1 is accompanied by the formation of a stable holocomplex between a Dβ-proximal promoter and Eβ. These findings indicate a stepwise process for Dβ → Jβ recombination that relies on distinct aspects of Eβ activity: an intrinsic function that directs general chromatin opening and a cooperative function that facilitates the assembly of a promoter/enhancer holocomplex, unmasks the Dβ1 gene segment, and triggers TCRβ gene assembly.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2006.02.009