Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation

作者：Morikawa Hiromasa; Ohkura Naganari; Vandenbon Alexis; Itoh Masayoshi; Nagao Sato Sayaka; Kawaji Hideya; Lassmann Timo; Carninci Piero; Hayashizaki Yoshihide; Forrest Alistair R R; Standley Daron M; Date Hiroshi; Sakaguchi Shimon^*

来源：Proceedings of the National Academy of Sciences, 2014, 111(14): 5289-5294.

DOI：10.1073/pnas.1312717110

Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression.

• 出版日期2014-4-8