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.
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, Ar; Standley, Dm; Date, H; Sakaguchi, S; FANTOM Consortium (Forrest, Ar; Kawaji, H; Rehli, M; Baillie, Jk; de Hoon, Mj; Haberle, V; Lassmann, T; Kulakovskiy, Iv; Lizio, M; Itoh, M; Andersson, R; Mungall, Cj; Meehan, Tf; Schmeier, S; Bertin, N; Jørgensen, M; Dimont, E; Arner, E; Schmidl, C; Schaefer, U; Medvedeva, Ya; Plessy, C; Vitezic, M; Severin, J; Semple, Ca; Ishizu, Y; Francescatto, M; Alam, I; Albanese, D; Altschuler, Gm; Archer, Ja; Arner, P; Babina, M; Baker, S; Balwierz, Pj; Beckhouse, Ag; Pradhan Bhatt, S; Blake, Ja; Blumenthal, A; Bodega, B; Bonetti, A; Briggs, J; Brombacher, F; Burroughs, Am; Califano, A; Cannistraci, Cv; Carbajo, D; Chen, Y; Chierici, M; Ciani, Y; Clevers, Hc; Dalla, E; Davis, Ca; Deplancke, B; Detmar, M; Diehl, Ad; Dohi, T; Drabløs, F; Edge, As; Edinger, M; Ekwall, K; Endoh, M; Enomoto, H; Fagiolini, M; Fairbairn, L; Fang, H; Farach Carson, Mc; Faulkner, Gj; Favorov, Av; Fisher, Me; Frith, Mc; Fujita, R; Fukuda, S; Furlanello, C; Furuno, M; Furusawa, J; Geijtenbeek, Tb; Gibson, A; Gingeras, T; Goldowitz, D; Gough, J; Guhl, S; Guler, R; Gustincich, Stefano; Ha, Tj; Hamaguchi, M; Hara, M; Harbers, M; Harshbarger, J; Hasegawa, A; Hasegawa, Y; Hashimoto, T; Herlyn, M; Hitchens, Kj; Ho Sui, Sj; Hofmann, Om; Hoof, I; Hori, F; Huminiecki, L; Iida, K; Ikawa, T; Jankovic, Br; Jia, H; Joshi, A; Jurman, G; Kaczkowski, B; Kai, C; Kaida, K; Kaiho, A; Kajiyama, K; Kanamori Katayama, M; Kasianov, As; Kasukawa, T; Katayama, S; Kato, S; Kawaguchi, S; Kawamoto, H; Kawamura, Yi; Kawashima, T; Kempfle, Js; Kenna, Tj; Kere, J; Khachigian, Lm; Kitamura, T; Klinken, Sp; Knox, Aj; Kojima, M; Kojima, S; Kondo, N; Koseki, H; Koyasu, S; Krampitz, S; Kubosaki, A; Kwon, At; Laros, Jf; Lee, W; Lennartsson, A; Li, K; Lilje, B; Lipovich, L; Mackay Sim, A; Manabe, R; Mar, Jc; Marchand, B; Mathelier, A; Mejhert, N; Meynert, A; Mizuno, Y; Morais, Da; Morikawa, H; Morimoto, M; Moro, K; Motakis, E; Motohashi, H; Mummery, Cl; Murata, M; Nagao Sato, S; Nakachi, Y; Nakahara, F; Nakamura, T; Nakamura, Y; Nakazato, K; van Nimwegen, E; Ninomiya, N; Nishiyori, H; Noma, S; Nozaki, T; Ogishima, S; Ohkura, N; Ohmiya, H; Ohno, H; Ohshima, M; Okada Hatakeyama, M; Okazaki, Y; Orlando, V; Ovchinnikov, Da; Pain, A; Passier, R; Patrikakis, M; Persson, H; Piazza, S; Prendergast, Jg; Rackham, Oj; Ramilowski, Ja; Rashid, M; Ravasi, T; Rizzu, P; Roncador, M; Roy, S; Rye, Mb; Saijyo, E; Sajantila, A; Saka, A; Sakaguchi, S; Sakai, M; Sato, H; Satoh, H; Savvi, S; Saxena, A; Schneider, C; Schultes, Ea; Schulze Tanzil, Gg; Schwegmann, A; Sengstag, T; Sheng, G; Shimoji, H; Shimoni, Y; Shin, Jw; Simon, C; Sugiyama, D; Sugiyama, T; Suzuki, M; Swoboda, Rk; 't Hoen, Pa; Tagami, M; Takahashi, N; Takai, J; Tanaka, H; Tatsukawa, H; Tatum, Z; Thompson, M; Toyoda, H; Toyoda, T; Valen, E; van de Wetering, M; van den Berg, Lm; Verardo, R; Vijayan, D; Vorontsov, Ie; Wasserman, Ww; Watanabe, S; Wells, Ca; Winteringham, Ln; Wolvetang, E; Wood, Ej; Yamaguchi, Y; Yamamoto, M; Yoneda, M; Yonekura, Y; Yoshida, S; Zabierowski, Se; Zhang, Pg; Zhao, X; Zucchelli, S; Summers, Km; Suzuki, H; Daub, Co; Kawai, J; Heutink, P; Hide, W; Freeman, Tc; Lenhard, B; Bajic, Vb; Taylor, Ms; Makeev, Vj; Sandelin, A; Hume, Da; Carninci, P; Hayashizaki, Y.. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 111:14(2014), pp. 5289-5294. [10.1073/pnas.1312717110]
Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation
Gustincich, Stefano;
2014-01-01
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.| File | Dimensione | Formato | |
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