TY - JOUR
T1 - Regulation of TCRβ Gene Assembly by a Promoter/Enhancer Holocomplex
AU - Oestreich, Kenneth J.
AU - Cobb, Robin Milley
AU - Pierce, Steven
AU - Chen, Jianzhu
AU - Ferrier, Pierre
AU - Oltz, Eugene M.
N1 - Funding Information:
We thank R. Schlimgen and M. Krangel for their helpful advice on 3C analyses. We also thank D. Ballard (Vanderbilt University) for many helpful comments and S. Hiebert (VU) for the RUNX1 antibody. This work was supported by the National Institutes of Health (P01 HL68744 and CA100905, E.M.O.; T32 HL69765, R.M.C.; T32 CA09385, K.J.O.) and a Cancer Center Support Grant (P30 CA68485, Vanderbilt-Ingram Cancer Center).
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=33646007633&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2006.02.009
DO - 10.1016/j.immuni.2006.02.009
M3 - Article
C2 - 16618597
AN - SCOPUS:33646007633
SN - 1074-7613
VL - 24
SP - 381
EP - 391
JO - Immunity
JF - Immunity
IS - 4
ER -