Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells

Yukiko Watanabe, Atsushi Onodera, Urara Kanai, Tomomi Ichikawa, Kazushige Obata-Ninomiya, Tomoko Wada, Masahiro Kiuchi, Chiaki Iwamura, Damon J. Tumes, Kenta Shinoda, Ryoji Yagi, Shinichiro Motohashi, Kiyoshi Hirahara, Toshinori Nakayama

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)12829-12834
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number35
DOIs
Publication statusPublished or Issued - 2 Sep 2014

Keywords

  • Asthma
  • Chromatin
  • RNAPII

ASJC Scopus subject areas

  • General

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