The DOI matches its Crossref record; 18 of the 19 references it cites were found in a registry or an index.
Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells
Abstract
Transcription factor Foxp3 (forkhead box P3), restricted in its expression to a specialized regulatory CD4+ T-cell subset (T(R)) with a dedicated suppressor function, controls T(R) lineage development. In humans and mice, Foxp3 deficiency results in a paucity of T(R) cells and a fatal breach in immunological tolerance, causing highly aggressive multi-organ autoimmune pathology. Here, through genome-wide analysis combining chromatin immunoprecipitation with mouse genome tiling array profiling, we identify Foxp3 binding regions for approximately 700 genes and for an intergenically encoded microRNA. We find that a large number of Foxp3-bound genes are up- or downregulated in Foxp3+ T cells, suggesting that Foxp3 acts as both a transcriptional activator and repressor. Foxp3-mediated regulation unique to the thymus affects, among others, genes encoding nuclear factors that control gene expression and chromatin remodelling. In contrast, Foxp3 target genes shared by the thymic and peripheral T(R) cells encode primarily plasma membrane proteins, as well as cell signalling proteins. Together, our studies suggest that distinct transcriptional sub-programmes implemented by Foxp3 establish T(R) lineage during differentiation and its proliferative and functional competence in the periphery.
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“The genes affected by either positive or negative regulators also significantly overlap with those bound by key CD4+ transcription factors (e.g., Foxp326,27, Batf, Irf4, and ROR-γt28,29, Xiao et al., unpublished data).”
From Dynamic regulatory network controlling TH17 cell differentiation (2013) · cites this paper as [27]
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Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745
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Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J., Farr, A. G., & Rudensky, A. Y. (2005) · Immunity · doi:10.1016/j.immuni.2005.01.016 · Cited by 2,302
Self-citationFoxp3+CD25+CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune disease
Sakaguchi, S., Ono, M., Setoguchi, R., Yagi, H., Hori, S., Fehervari, Z. T., Shimizu, J., Takahashi, T., & Nomura, T. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00427.x · Cited by 1,589
Accumulation of miR-155 and BIC RNA in human B cell lymphomas
Eis, P. S., Tam, W., Sun, L., Chadburn, A., Li, Z., Gomez, M. F., Lund, E., & Dahlberg, J. E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500613102 · Cited by 1,322
FOXP3 Controls Regulatory T Cell Function through Cooperation with NFAT
Wu, Y., Borde, M., Heissmeyer, V., Feuerer, M., Lapan, A. D., Stroud, J. C., Bates, D. L., Guo, L., Han, A., Ziegler, S. F., et al. (2006) · Cell · doi:10.1016/j.cell.2006.05.042 · Cited by 1,229
Foxp3-dependent programme of regulatory T-cell differentiation
Gavin, M. A., Rasmussen, J. P., Fontenot, J. D., Vasta, V., Manganiello, V. C., Beavo, J. A., & Rudensky, A. Y. (2007) · Nature · doi:10.1038/nature05543 · Cited by 1,127
Self-citationZhang, X., Odom, D. T., Koo, S.-H., Conkright, M. D., Canettieri, G., Best, J., Chen, H., Jenner, R., Herbolsheimer, E., Jacobsen, E., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501076102 · Cited by 992
Fontenot, J. D., & Rudensky, A. Y. (2005) · Nature Immunology · doi:10.1038/ni1179 · Cited by 957
Self-citationPre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice
Costinean, S., Zanesi, N. A. O., Pekarsky, Y., Tili, E., Volinia, S., Heerema, N. A., & Croce, C. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602266103 · Cited by 952
Ziegler, S. F. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090547 · Cited by 921
Homeostasis and anergy of CD4+CD25+ suppressor T cells in vivo
Gavin, M. A., Clarke, S. R. M., Negrou, E., Gallegos, A. M., & Rudensky, A. Y. (2001) · Nature Immunology · doi:10.1038/ni743 · Cited by 643
Self-citationA role for Dicer in immune regulation
Cobb, B. S., Hertweck, A., Smith, J. C., O’Connor, E., Graf, D., Cook, T. H., Smale, S. T., Sakaguchi, S., Livesey, F. J., Fisher, A. G., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061692 · Cited by 533
Model-based analysis of tiling-arrays for ChIP-chip
Johnson, W. E., Li, W., Meyer, C. A., Gottardo, R., Carroll, J. S., Brown, M. A., & Liu, X. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601180103 · Cited by 428
Chen, C., Rowell, E. A., Thomas, R. M., Hancock, W. W., & Wells, A. D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608848200 · Cited by 233
Strategies and tools for whole-genome alignments
Couronne, O., Poliakov, A., Bray, N., Ishkhanov, T., Ryaboy, D., Rubin, E., Pachter, L., & Dubchak, I. (2003) · Genome Research · doi:10.1101/gr.762503 · Cited by 224
Tam, W., Hughes, S. H., Hayward, W. S., & Besmer, P. (2002) · Journal of Virology · doi:10.1128/jvi.76.9.4275-4286.2002 · Cited by 151
Beima, K. M., Miazgowicz, M. M., Lewis, M. D., Yan, P. S., Huang, T. H. ‐., & Weinmann, A. S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513613200 · Cited by 135
Michael, L. F., Asahara, H., Shulman, A. I., Kraus, W. L., & Montminy, M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.5.1596-1603.2000 · Cited by 104
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1 of the 19 references couldn’t be matched to a known paper.
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Regulatory T Cells and Immune Tolerance
Sakaguchi, S., Yamaguchi, T., Nomura, T., & Ono, M. (2008) · Cell · doi:10.1016/j.cell.2008.05.009 · Cited by 5,475
CTLA-4 Control over Foxp3 + Regulatory T Cell Function
Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., & Sakaguchi, S. (2008) · Science · doi:10.1126/science.1160062 · Cited by 2,956
Regulatory T cells: mechanisms of differentiation and function
Josefowicz, S. Z., Lu, L.-F., & Rudensky, A. Y. (2012) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141623 · Cited by 2,866
Self-citationRegulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces
Rubtsov, Y. P., Rasmussen, J. P., Chi, E. Y., Fontenot, J., Castelli, L., Ye, X., Treuting, P., Siewe, L., Roers, A., Henderson, W. R., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.017 · Cited by 1,586
Self-citationA census of human transcription factors: function, expression and evolution
Vaquerizas, J. M., Kummerfeld, S. K., Teichmann, S. A., & Luscombe, N. M. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2538 · Cited by 1,573
Metadata
- Authors
- Zheng, Y., Josefowicz, S. Z., Kas, A., Chu, T.-T., Gavin, M. A., & Rudensky, A. Y.
- Affiliations
- University of Washington (US)
- Amgen (United States) (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Rudensky, Alexander Y.
- Venue
- Nature
- Published
- 2007-01-21
- Volume
- 445
- Issue
- 7130
- Pages
- 936-940
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1992641327
- Cited by
- 835
- References
- 19
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 22 · 2023: 17 · 2022: 26 · 2021: 30 · 2020: 36 · 2019: 48 · 2018: 36 · 2017: 37 · 2016: 32 · 2015: 40 · 2014: 49 · 2013: 62 · 2012: 63
- FWCI
- 31.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Cancer Research Institute
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- Foxp3, regulatory T cells, transcriptional regulation, chromatin binding, microRNA, thymic Treg development, chromatin remodeling, nuclear transcription factors, immune tolerance, autoimmune disease, CD4+ T cells
- MeSH terms
- Animals, Cell Differentiation, Gene Expression Regulation, Mice, Inbred C57BL, Protein Binding, Thymus Gland, Genome, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Genomics, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors
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