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

Morikawa, Hiromasa, Ohkura, Naganari, Vandenbon, Alexis, Itoh, Masayoshi, Nagao-Sato, Sayaka, Kawaji, Hideya, Lassman, Timo, Carninci, Piero, Hayashizaki, Yoshihide, Forrest, Alistair R. R., Standley, Daron M., Date, Hiroshi, Sakaguchi, Shimon and the FANTOM Consortium (2014) Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. Proceedings of the National Academy of Sciences of the United States of America, 111 14: 5289-5294. doi:10.1073/pnas.1312717110

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Author Morikawa, Hiromasa
Ohkura, Naganari
Vandenbon, Alexis
Itoh, Masayoshi
Nagao-Sato, Sayaka
Kawaji, Hideya
Lassman, Timo
Carninci, Piero
Hayashizaki, Yoshihide
Forrest, Alistair R. R.
Standley, Daron M.
Date, Hiroshi
Sakaguchi, Shimon
the FANTOM Consortium
Title Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2014-04-08
Year available 2014
Sub-type Article (original research)
DOI 10.1073/pnas.1312717110
Open Access Status Not Open Access
Volume 111
Issue 14
Start page 5289
End page 5294
Total pages 6
Place of publication Washington, United States
Publisher National Academy of Sciences
Language eng
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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 20002007
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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Created: Thu, 26 Jun 2014, 21:03:50 EST by Cathy Fouhy on behalf of Aust Institute for Bioengineering & Nanotechnology