TY - JOUR
T1 - Regulation of T Cell Receptor β Gene Rearrangements and Allelic Exclusion by the Helix-Loop-Helix Protein, E47
AU - Agata, Yasutoshi
AU - Tamaki, Nobuyuki
AU - Sakamoto, Shuji
AU - Ikawa, Tomokatsu
AU - Masuda, Kyoko
AU - Kawamoto, Hiroshi
AU - Murre, Cornelis
N1 - Funding Information:
We thank T. Honjo, Y. Wakatsuki, T. Okazaki, and M. Yamori for providing the mice, N. Minato and M. Hattori for animal facility, T. Kitamura for providing Plat-E cells, Y. Kaziro, K. Ikuta, H. Kimura, K. Maki, I. Yanagihara, D. Suzuki, S. Yamasaki, M. Moriyama, and members of the Murre lab and Horizontal Medical Research Organization for discussions and materials, K. Kotera for technical assistance, and I. Engel and D. Suzuki for critical reading of the manuscript. This work was supported by grants from the Special Coordination Funds for Promoting Science and Technology; the Ministry of Education, Culture, Sports, Science, and Technology of Japan; and the Uehara Memorial Foundation (Y.A.). Y.A. was supported in part by a fellowship from Japan Science and Technology. C.M., Y.A., and T.I. were supported by funding from the National Institutes of Health.
PY - 2007/12/21
Y1 - 2007/12/21
N2 - Allelic exclusion of antigen-receptor genes is ensured primarily by monoallelic locus activation upon rearrangement and subsequently by feedback inhibition of continued rearrangement. Here, we demonstrated that the basic helix-loop-helix protein, E47, promoted T cell receptor β (TCRβ) gene rearrangement by directly binding to target gene segments to increase chromatin accessibility in a dosage-sensitive manner. Feedback signaling abrogated E47 binding, leading to a decline in accessibility. Conversely, enforced expression of E47 induced TCRβ gene rearrangement by antagonizing feedback inhibition. Thus, the abundance of E47 is rate limiting in locus activation, and feedback signaling downregulates E47 activity to ensure allelic exclusion.
AB - Allelic exclusion of antigen-receptor genes is ensured primarily by monoallelic locus activation upon rearrangement and subsequently by feedback inhibition of continued rearrangement. Here, we demonstrated that the basic helix-loop-helix protein, E47, promoted T cell receptor β (TCRβ) gene rearrangement by directly binding to target gene segments to increase chromatin accessibility in a dosage-sensitive manner. Feedback signaling abrogated E47 binding, leading to a decline in accessibility. Conversely, enforced expression of E47 induced TCRβ gene rearrangement by antagonizing feedback inhibition. Thus, the abundance of E47 is rate limiting in locus activation, and feedback signaling downregulates E47 activity to ensure allelic exclusion.
UR - http://www.scopus.com/inward/record.url?scp=37049009268&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37049009268&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2007.11.015
DO - 10.1016/j.immuni.2007.11.015
M3 - Article
C2 - 18093539
AN - SCOPUS:37049009268
SN - 1074-7613
VL - 27
SP - 871
EP - 884
JO - Immunity
JF - Immunity
IS - 6
ER -
