Open AccessThe Cxxc1 subunit of the Trithorax complex directs epigenetic licensing of CD4+ T cell differentiation
Author(s) -
Masahiro Kiuchi,
Atsushi Onodera,
Kota Kokubo,
Tomomi Ichikawa,
Yuki Morimoto,
Eiryo Kawakami,
Nobuki Takayama,
Koji Eto,
Haruhiko Koseki,
Kiyoshi Hirahara,
Toshinori Nakayama
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20201690
Subject(s) - biology , epigenetics , t cell , t cell receptor , cellular differentiation , microbiology and biotechnology , gene , context (archaeology) , transcription factor , immune system , regulation of gene expression , genetics , paleontology
Different dynamics of gene expression are observed during cell differentiation. In T cells, genes that are turned on early or turned off and stay off have been thoroughly studied. However, genes that are initially turned off but then turned on again after stimulation has ceased have not been defined; they are obviously important, especially in the context of acute versus chronic inflammation. Using the Th1/Th2 differentiation paradigm, we found that the Cxxc1 subunit of the Trithorax complex directs transcription of genes initially down-regulated by TCR stimulation but up-regulated again in a later phase. The late up-regulation of these genes was impaired either by prolonged TCR stimulation or Cxxc1 deficiency, which led to decreased expression of Trib3 and Klf2 in Th1 and Th2 cells, respectively. Loss of Cxxc1 resulted in enhanced pathogenicity in allergic airway inflammation in vivo. Thus, Cxxc1 plays essential roles in the establishment of a proper CD4+ T cell immune system via epigenetic control of a specific set of genes.