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

• DOI: 10.1073/pnas.1312717110
• Publication Date: 2014-03-28T10:48:18Z
• Authors: Hiromasa Morikawa; Naganari Ohkura; Alexis Vandenbon; Masayoshi Itoh; Sayaka Nagao-Sato; Hideya Kawaji; Timo Lassmann; Piero Carninci; Yoshihide Hayashi...; Alistair R. R. Fo...; Daron M. Standley; Hiroshi Date; Shimon Sakaguchi; ; Alistair R.R. For...; Hideya Kawaji; Michael Rehli; J. Kenneth Baillie; Michiel J.L. de Hoon; Vanja Haberle; Timo Lassmann; Ivan V. Kulakovskiy; Marina Lizio; Masayoshi Itoh; Robin Andersson; Christopher J. Mu...; Terrence F. Meehan; Sebastian Schmeier; Nicolas Bertin; Mette Jørgensen; Emmanuel Dimont; Erik Arner; Christian Schmidl; Ulf Schaefer; Yulia A. Medvedeva; Charles Plessy; Morana Vitezic; Jessica Severin; Colin A. Semple; Yuri Ishizu; Margherita France...; Intikhab Alam; Davide Albanese; Gabriel M. Altsch...; John A.C. Archer; Peter Arner; Magda Babina; Sarah Baker; Piotr J. Balwierz; Anthony G. Beckhouse; Swati Pradhan-Bhatt; Judith A. Blake; Antje Blumenthal; Beatrice Bodega; Alessandro Bonetti; James Briggs; Frank Brombacher; A. Maxwell Burroughs; Andrea Califano; Carlo V. Cannistraci; Daniel Carbajo; Yun Chen; Marco Chierici; Yari Ciani; Hans C. Clevers; Emiliano Dalla; Carrie A. Davis; Bart Deplancke; Michael Detmar; Alexander D. Diehl; Taeko Dohi; Finn Drabløs; Albert S.B. Edge; Matthias Edinger; Karl Ekwall; Mitsuhiro Endoh; Hideki Enomoto; Michela Fagiolini; Lynsey Fairbairn; Hai Fang; Mary C. Farach-Ca...; Geoffrey J. Faulkner; Alexander V. Favorov; Malcolm E. Fisher; Martin C. Frith; Rie Fujita; Shiro Fukuda; Cesare Furlanello; Masaaki Furuno; Jun-ichi Furusawa; Teunis B. Geijten...; Andrew Gibson; Thomas Gingeras; Daniel Goldowitz; Julian Gough; Sven Guhl; Reto Guler; Stefano Gustincich; Thomas J. Ha; Masahide Hamaguchi; Mitsuko Hara; Matthias Harbers; Jayson Harshbarger; Akira Hasegawa; Yuki Hasegawa; Takehiro Hashimoto; Meenhard Herlyn; Kelly J. Hitchens; Shannan J. Ho Sui; Oliver M. Hofmann; Ilka Hoof; Fumi Hori; Lukasz Huminiecki; Kei Iida; Tomokatsu Ikawa; Boris R. Jankovic; Hui Jia; Anagha Joshi; Giuseppe Jurman; Bogumil Kaczkowski; Chieko Kai; Kaoru Kaida; Ai Kaiho; Kazuhiro Kajiyama; Mutsumi Kanamori-...; Artem S. Kasianov; Takeya Kasukawa; Shintaro Katayama; Sachi Kato; Shuji Kawaguchi; Hiroshi Kawamoto; Yuki I. Kawamura; Tsugumi Kawashima; Judith S. Kempfle; Tony J. Kenna; Juha Kere; Levon M. Khachigian; Toshio Kitamura; S. Peter Klinken; Alan J. Knox; Miki Kojima; Soichi Kojima; Naoto Kondo; Haruhiko Koseki; Shigeo Koyasu; Sarah Krampitz; Atsutaka Kubosaki; Andrew T. Kwon; Jeroen F.J. Laros; Weonju Lee; Andreas Lennartsson; Kang Li; Berit Lilje; Leonard Lipovich; Alan Mackay-sim; Ri-ichiroh Manabe; Jessica C. Mar; Benoit Marchand; Anthony Mathelier; Niklas Mejhert; Alison Meynert; Yosuke Mizuno; David A. de Lima ...; Hiromasa Morikawa; Mitsuru Morimoto; Kazuyo Moro; Efthymios Motakis; Hozumi Motohashi; Christine L. Mummery; Mitsuyoshi Murata; Sayaka Nagao-Sato; Yutaka Nakachi; Fumio Nakahara; Toshiyuki Nakamura; Yukio Nakamura; Kenichi Nakazato; Erik van Nimwegen; Noriko Ninomiya; Hiromi Nishiyori; Shohei Noma; Tadasuke Nozaki; Soichi Ogishima; Naganari Ohkura; Hiroko Ohmiya; Hiroshi Ohno; Mitsuhiro Ohshima; Mariko Okada-Hata...; Yasushi Okazaki; Valerio Orlando; Dmitry A. Ovchinn...; Arnab Pain; Robert Passier; Margaret Patrikakis; Helena Persson; Silvano Piazza; James G.D. Prende...; Owen J.L. Rackham; Jordan A. Ramilowski; Mamoon Rashid; Timothy Ravasi; Patrizia Rizzu; Marco Roncador; Sugata Roy; Morten B. Rye; Eri Saijyo; Antti Sajantila; Akiko Saka; Shimon Sakaguchi; Mizuho Sakai; Hiroki Sato; Hironori Satoh; Suzana Savvi; Alka Saxena; Claudio Schneider; Erik A. Schultes; Gundula G. Schulz...; Anita Schwegmann; Thierry Sengstag; Guojun Sheng; Hisashi Shimoji; Yishai Shimoni; Jay W. Shin; Christophe Simon; Daisuke Sugiyama; Takaaki Sugiyama; Masanori Suzuki; Rolf K. Swoboda; Peter A.C. 't Hoen; Michihira Tagami; Naoko Takahashi; Jun Takai; Hiroshi Tanaka; Hideki Tatsukawa; Zuotian Tatum; Mark Thompson; Hiroo Toyoda; Tetsuro Toyoda; Eivind Valen; Marc van de Wetering; Linda M. van den ...; Roberto Verardo; Dipti Vijayan; Ilya E. Vorontsov; Wyeth W. Wasserman; Shoko Watanabe; Christine A. Wells; Louise N. Winteri...; Ernst Wolvetang; Emily J. Wood; Yoko Yamaguchi; Masayuki Yamamoto; Misako Yoneda; Yohei Yonekura; Shigehiro Yoshida; Suzan E. Zabierowski; Peter G. Zhang; Xiaobei Zhao; Silvia Zucchelli; Kim M. Summers; Harukazu Suzuki; Carsten O. Daub; Jun Kawai; Peter Heutink; Winston Hide; Tom C. Freeman; Boris Lenhard; Vladimir B. Bajic; Martin S. Taylor; Vsevolod J. Makeev; Albin Sandelin; David A. Hume; Piero Carninci; Yoshihide Hayashi...
• Keywords: 570; Transcription, Genetic; T-Lymphocytes; 610; Down-Regulation; Inbred C57BL; T-Lymphocytes, Regulatory; Epigenesis, Genetic; Mice; 03 medical and health sciences; 0302 clinical medicine; Genetic; Medicine and Health Sciences; Animals; Inbred BALB C; Mice, Inbred BALB C; Binding Sites; Life Sciences; Forkhead Transcription Factors; DNA Methylation; Regulatory; Multidisciplinary Sciences; Mice, Inbred C57BL; Gene Expression Regulation; 1000 General; Science & Technology - Other Topics; Transcription; Epigenesis

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