Abstract
Regulatory T (Treg) cells play a key role in dominant suppression of immune response and maintenance of immune homeostasis. Foxp3, a member of the forkhead transcription factor family, is indispensable for Treg cell development and function. Mice and human with Foxp3 mutations are severely impaired in Treg cell generation and develop lethal autoimmune diseases. We combined chromatin immuno-precipitation and mouse whole genome tiling array profiling (ChIP-on-Chip) to identify the direct downstream targets of Foxp3 in regulatory T cells. Our result showed that Foxp3 not only directly determines expression of a number of Treg signature molecules, but also regulates a group of transcription factors, which potentially control the expression of other Treg-specific genes.
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References
Sakaguchi S, Yamaguchi T, Nomura T, Ono M. 2008. Regulatory T cells and immune tolerance. Cell 133: 775–87
Zheng Y, Rudensky AY. 2007. Foxp3 in control of the regulatory T cell lineage. Nat Immunol 8: 457–62
Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, Wilkinson JE, Galas D, Ziegler SF, Ramsdell F. 2001. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 27: 68–73
Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD. 2001. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27: 20–1
Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, Levy-Lahad E, Mazzella M, Goulet O, Perroni L, Bricarelli FD, Byrne G, McEuen M, Proll S, Appleby M, Brunkow ME. 2001. X-linked Âneonatal diabetes mellitus, enteropathy and Âendocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 27: 18–20
Hori S, Nomura T, Sakaguchi S. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057–61
Fontenot JD, Gavin MA, Rudensky AY. 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4: 330–6
Zheng Y, Josefowicz SZ, Kas A, Chu TT, Gavin MA, Rudensky AY. 2007. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 445: 936–40
Marson A, Kretschmer K, Frampton GM, Jacobsen ES, Polansky JK, MacIsaac KD, Levine SS, Fraenkel E, von Boehmer H, Young RA. 2007. Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445: 931–5
Johnson WE, Li W, Meyer CA, Gottardo R, Carroll JS, Brown M, Liu XS. 2006. Model-based analysis of tiling-arrays for ChIP-chip. Proc Natl Acad Sci U S A 103: 12457–62
Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, Chen H, Jenner R, Herbolsheimer E, Jacobsen E, Kadam S, Ecker JR, Emerson B, Hogenesch JB, Unterman T, Young RA, Montminy M. 2005. Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci U S A 102: 4459–64
Acknowledgments
The author would like to thank Professor Alexander Rudensky for his advice and support for this project, Steven Josefowicz for help and discussion, Arnold Kas for bioinformatics analysis, and Wei Li and Shirley Liu for assistance on MAT program. This work was supported by Cancer Research Institute and National Institute of Health (NIH).
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Zheng, Y. (2011). ChIP-on-Chip for FoxP3. In: Kassiotis, G., Liston, A. (eds) Regulatory T Cells. Methods in Molecular Biology, vol 707. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61737-979-6_6
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DOI: https://doi.org/10.1007/978-1-61737-979-6_6
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