Silencing of the Il2 gene transcription is regulated by epigenetic changes in anergic T cells
作者： Sanmay Bandyopadhyay , Cristina Montagna , Fernando Macian
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摘要: Anergy is induced in T cells as a consequence of partial or suboptimal stimulation. Anergic become unresponsive and fail to proliferate produce cytokines. We had previously shown that anergic CD4+ cells, Ikaros participates the transcriptional repression Il2 gene by recruiting histone deacetylases cause core deacetylation at promoter. Here we show promoter initial step process leads stable silencing transcription cells. have found anergy-induced permits binding methyl-transferase Suv39H1, which trimethylates lysine-9 H3 (Me3H3-K9). Furthermore, establishment Me3H3-K9 mark allows recruitment heterochromatin protein HP1, allowing silenced loci reposition close heterochromatin-rich regions. Our results indicate attained through series epigenetic changes involve repressive marks subsequent nuclear repositioning loci, juxtaposed transcriptionally silent This mechanism may account for nature inhibition IL-2 production
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sci-hub.se 参考文章(63)
Andrew J. Bannister, Philip Zegerman, Janet F. Partridge, Eric A. Miska, Jean O. Thomas, Robin C. Allshire, Tony Kouzarides, Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature. ,vol. 410, pp. 120- 124 ,(2001) , 10.1038/35065138
Ichiro Taniuchi, Wilfried Ellmeier, Dan R Littman, The CD4/CD8 lineage choice: new insights into epigenetic regulation during T cell development. Advances in Immunology. ,vol. 83, pp. 55- 89 ,(2004) , 10.1016/S0065-2776(04)83002-5
Marc K Jenkins, CA Chen, Grace Jung, Daniel L Mueller, Ronald H Schwartz, Inhibition of antigen-specific proliferation of type 1 murine T cell clones after stimulation with immobilized anti-CD3 monoclonal antibody. Journal of Immunology. ,vol. 144, pp. 16- 22 ,(1990)
Monika Lachner, Dónal O'Carroll, Stephen Rea, Karl Mechtler, Thomas Jenuwein, Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature. ,vol. 410, pp. 116- 120 ,(2001) , 10.1038/35065132
Gwen Lomberk, Lori Wallrath, Raul Urrutia, The Heterochromatin Protein 1 family Genome Biology. ,vol. 7, pp. 228- 228 ,(2006) , 10.1186/GB-2006-7-7-228
Rajan M. Thomas, Neelanjana Chunder, Chunxia Chen, Sarah E. Umetsu, Susan Winandy, Andrew D. Wells, Ikaros Enforces the Costimulatory Requirement for IL2 Gene Expression and Is Required for Anergy Induction in CD4+ T Lymphocytes The Journal of Immunology. ,vol. 179, pp. 7305- 7315 ,(2007) , 10.4049/JIMMUNOL.179.11.7305
Rajan M. Thomas, Ling Gao, Andrew D. Wells, Signals from CD28 Induce Stable Epigenetic Modification of the IL-2 Promoter The Journal of Immunology. ,vol. 174, pp. 4639- 4646 ,(2005) , 10.4049/JIMMUNOL.174.8.4639
R M Thomas, S J Saouaf, A D Wells, Superantigen-induced CD4+ T cell tolerance is associated with DNA methylation and histone hypo-acetylation at cytokine gene loci. Genes and Immunity. ,vol. 8, pp. 613- 618 ,(2007) , 10.1038/SJ.GENE.6364415
Alexander J. Ruthenburg, Haitao Li, Dinshaw J. Patel, C. David Allis, Multivalent engagement of chromatin modifications by linked binding modules Nature Reviews Molecular Cell Biology. ,vol. 8, pp. 983- 994 ,(2007) , 10.1038/NRM2298
Karen E Brown, Simon S Guest, Stephen T Smale, Kyungmin Hahm, Matthias Merkenschlager, Amanda G Fisher, Association of Transcriptionally Silent Genes with Ikaros Complexes at Centromeric Heterochromatin Cell. ,vol. 91, pp. 845- 854 ,(1997) , 10.1016/S0092-8674(00)80472-9