Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation.
Document Type
Article
Publication Date
4-8-2014
JAX Source
Proc Natl Acad Sci U S A 2014 Apr 8; 111(14):5289-5294.
Volume
111
Issue
14
First Page
5289
Last Page
5294
ISSN
1091-6490
PMID
24706905
Abstract
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. Proc Natl Acad Sci U S A 2014 Apr 8; 111(14):5289-5294.
Recommended Citation
Morikawa H,
Ohkura N,
Vandenbon A,
Itoh M,
Nagao-Sato S,
Kawaji H,
Lassmann T,
Carninci P,
Hayashizaki Y,
Forrest A,
Standley D,
Date H,
Sakaguchi S,
Consortium F.
Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. Proc Natl Acad Sci U S A 2014 Apr 8; 111(14):5289-5294.