TY - JOUR
T1 - Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells
AU - Watanabe, Yukiko
AU - Onodera, Atsushi
AU - Kanai, Urara
AU - Ichikawa, Tomomi
AU - Obata-Ninomiya, Kazushige
AU - Wada, Tomoko
AU - Kiuchi, Masahiro
AU - Iwamura, Chiaki
AU - Tumes, Damon J.
AU - Shinoda, Kenta
AU - Yagi, Ryoji
AU - Motohashi, Shinichiro
AU - Hirahara, Kiyoshi
AU - Nakayama, Toshinori
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/9/2
Y1 - 2014/9/2
N2 - Epigenetic modifications, such as posttranslational modifications of histones, play an important role in gene expression and regulation. These modifications are in part mediated by the Trithorax group (TrxG) complex and the Polycomb group (PcG) complex, which activate and repress transcription, respectively. We herein investigate the role of Menin, a component of the TrxG complex in T helper (Th) cell differentiation and show a critical role for Menin in differentiation and maintenance of Th17 cells. Menin-/- T cells do not efficiently differentiate into Th17 cells, leaving Th1 and Th2 cell differentiation intact in in vitro cultures. Menin deficiency resulted in the attenuation of Th17-induced airway inflammation. In differentiating Th17 cells, Menin directly bound to the Il17a gene locus and was required for the deposition of permissive histone modifications and recruitment of the RNA polymerase II transcriptional complex. Interestingly, although Menin bound to the Rorc locus, Menin was dispensable for the induction of Rorc expression and permissive histone modifications in differentiating Th17 cells. In contrast, Menin was required to maintain expression of Rorc in differentiated Th17 cells, indicating that Menin is essential to stabilize expression of the Rorc gene. Thus, Menin orchestrates Th17 cell differentiation and function by regulating both the induction and maintenance of target gene expression.
AB - Epigenetic modifications, such as posttranslational modifications of histones, play an important role in gene expression and regulation. These modifications are in part mediated by the Trithorax group (TrxG) complex and the Polycomb group (PcG) complex, which activate and repress transcription, respectively. We herein investigate the role of Menin, a component of the TrxG complex in T helper (Th) cell differentiation and show a critical role for Menin in differentiation and maintenance of Th17 cells. Menin-/- T cells do not efficiently differentiate into Th17 cells, leaving Th1 and Th2 cell differentiation intact in in vitro cultures. Menin deficiency resulted in the attenuation of Th17-induced airway inflammation. In differentiating Th17 cells, Menin directly bound to the Il17a gene locus and was required for the deposition of permissive histone modifications and recruitment of the RNA polymerase II transcriptional complex. Interestingly, although Menin bound to the Rorc locus, Menin was dispensable for the induction of Rorc expression and permissive histone modifications in differentiating Th17 cells. In contrast, Menin was required to maintain expression of Rorc in differentiated Th17 cells, indicating that Menin is essential to stabilize expression of the Rorc gene. Thus, Menin orchestrates Th17 cell differentiation and function by regulating both the induction and maintenance of target gene expression.
KW - Asthma
KW - Chromatin
KW - RNAPII
UR - http://www.scopus.com/inward/record.url?scp=84907228248&partnerID=8YFLogxK
U2 - 10.1073/pnas.1321245111
DO - 10.1073/pnas.1321245111
M3 - Article
C2 - 25136117
AN - SCOPUS:84907228248
SN - 0027-8424
VL - 111
SP - 12829
EP - 12834
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 35
ER -