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  Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation

Beyer, M., Thabet, Y., Müller, R. U., Sadlon, T., Classen, S., Lahl, K., et al. (2011). Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation. Nature Immunology, 12(9), 898-907. doi:10.1038/ni.2084.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-642C-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-642D-E
Genre: Journal Article

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 Creators:
Beyer, M., Author
Thabet, Y., Author
Müller, R. U., Author
Sadlon, T., Author
Classen, S., Author
Lahl, K., Author
Basu, S., Author
Zhou, X., Author
Bailey-Bucktrout, S. L., Author
Krebs, W., Author
Schönfeld, E. A., Author
Böttcher, J., Author
Golovina, T., Author
Mayer, C. T., Author
Hofmann, A., Author
Sommer, D., Author
Debey-Pascher, S., Author
Endl, E., Author
Limmer, A., Author
Hippen, K. L., Author
Blazar, B. R., AuthorBalderas, R., AuthorQuast, T., AuthorWaha, A., AuthorMayer, G., AuthorFamulok, M.1, AuthorKnolle, P. A., AuthorWickenhauser, C., AuthorKolanus, W., AuthorSchermer, B., AuthorBluestone, J. A., AuthorBarry, S. C., AuthorSparwasser, T., AuthorRiley, J. L., AuthorSchultze, J. L., Author more..
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1External Organizations, ou_persistent22              

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Free keywords: 3' Untranslated Regions/genetics/immunology Animals Cell Differentiation/drug effects Chromatin Assembly and Disassembly/drug effects/*immunology Flow Cytometry Forkhead Transcription Factors/genetics/*immunology/metabolism Gene Expression Profiling *Gene Expression Regulation Genome, Human Genome-Wide Association Study Humans Lentivirus Lymphocyte Activation/drug effects Matrix Attachment Region Binding Proteins/genetics/*immunology/metabolism Mice Mice, Inbred C57BL Mice, Knockout MicroRNAs/immunology/metabolism/pharmacology RNA Interference RNA, Small Interfering/immunology/metabolism/pharmacology Reverse Transcriptase Polymerase Chain Reaction *Self Tolerance/drug effects/genetics/immunology T-Lymphocytes, Regulatory/cytology/*immunology/metabolism Transduction, Genetic
 Abstract: Regulatory T cells (T(reg) cells) are essential for self-tolerance and immune homeostasis. Lack of effector T cell (T(eff) cell) function and gain of suppressive activity by T(reg) cells are dependent on the transcriptional program induced by Foxp3. Here we report that repression of SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T(reg) cells. Foxp3, acting as a transcriptional repressor, directly suppressed the SATB1 locus and indirectly suppressed it through the induction of microRNAs that bound the SATB1 3' untranslated region. Release of SATB1 from the control of Foxp3 in T(reg) cells caused loss of suppressive function, establishment of transcriptional T(eff) cell programs and induction of T(eff) cell cytokines. Our data support the proposal that inhibition of SATB1-mediated modulation of global chromatin remodeling is pivotal for maintaining T(reg) cell functionality.

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 Dates: 2011
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: Other: 21841785
DOI: 10.1038/ni.2084
ISSN: 1529-2916 (Electronic)
ISSN: 1529-2908 (Linking)
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Title: Nature Immunology
  Alternative Title : Nat. Immunol.
Source Genre: Journal
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Pages: - Volume / Issue: 12 (9) Sequence Number: - Start / End Page: 898 - 907 Identifier: -