Journal article

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

Hiromasa Morikawa, Naganari Ohkura, Alexis Vandenbon, Masayoshi Itoh, Sayaka Nagao-Sato, Hideya Kawaji, Timo Lassmann, Piero Carninci, Yoshihide Hayashizaki, Alistair RR Forrest, Daron M Standley, Hiroshi Date, Shimon Sakaguchi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2014

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 b..

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University of Melbourne Researchers

Grants

Awarded by Specially Promoted Research Grant-in-Aid


Awarded by Biotechnology and Biological Sciences Research Council


Awarded by BBSRC


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

We thank R. Ishii for technical assistance, all members of the FANTOM5 Consortium for contributing to generation of samples and analysis of the dataset, and Genome Network Analysis Support Facility (GeNAS) for data production. This work was supported by Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) to the RIKEN Center for Life Science Technologies, to RIKEN Preventive Medicine and Diagnosis Innovation Program (to Y.H.), and to RIKEN Omics Science Center (to Y.H.); a grant of the Innovative Cell Biology by Innovative Technology (Cell Innovation Program) from MEXT (to Y.H.); and by Core Research for Evolutional Science and Technology (to S. S.) and Specially Promoted Research Grant-in-Aid 20002007 (to S.S.).