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

Morikawa, H., Ohkura, N., Vandenbon, A., Itoh, M., Nagao-Sato, S., Kawaji, H., Lassmann, T., Carninci, P., Hayashizaki, Y., Forrest, A. R., Standley, D. M., Date, H., Sakaguchi, S., FANTOM Consortium (April 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). pp. 5289-94. ISSN 0027-8424

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URL: http://www.ncbi.nlm.nih.gov/pubmed/24706905

DOI: 10.1073/pnas.1312717110

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.

Item Type:	Paper
Uncontrolled Keywords:	Animals Binding Sites DNA Methylation Down-Regulation Epigenesis, Genetic Forkhead Transcription Factors/metabolism Gene Expression Regulation Mice Mice, Inbred BALB C Mice, Inbred C57BL T-Lymphocytes, Regulatory/metabolism *Transcription, Genetic
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics
CSHL Authors:	Gingeras, Thomas R. Davis, Carrie A.
Communities:	CSHL Cancer Center Program > Gene Regulation and Cell Proliferation CSHL labs > Gingeras lab
Depositing User:	Matt Covey
Date:	8 April 2014
Date Deposited:	13 Oct 2015 15:55
Last Modified:	20 Dec 2017 21:26
PMCID:	PMC3986152
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/31918

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