@article{e91ce3a80b1448c1ad52fcc5c3dbdffe,
title = "TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4 + T cell fate and interact with Runx3 to silence Cd4 in CD8 + T cells",
abstract = "The transcription factors TCF-1 and LEF-1 are essential for early T cell development, but their roles beyond the CD4 + CD8 + double-positive (DP) stage are unknown. By specific ablation of these factors in DP thymocytes, we demonstrated that deficiency in TCF-1 and LEF-1 diminished the output of CD4 + T cells and redirected CD4 + T cells to a CD8 + T cell fate. The role of TCF-1 and LEF-1 in the CD4-versus-CD8 lineage 'choice' was mediated in part by direct positive regulation of the transcription factor Th-POK. Furthermore, loss of TCF-1 and LEF-1 unexpectedly caused derepression of CD4 expression in T cells committed to the CD8 + lineage without affecting the expression of Runx transcription factors. Instead, TCF-1 physically interacted with Runx3 to cooperatively silence Cd4. Thus, TCF-1 and LEF-1 adopted distinct genetic 'wiring' to promote the CD4 + T cell fate and establish CD8 + T cell identity.",
author = "Steinke, {Farrah C.} and Shuyang Yu and Xinyuan Zhou and Bing He and Wenjing Yang and Bo Zhou and Hiroshi Kawamoto and Jun Zhu and Kai Tan and Xue, {Hai Hui}",
note = "Funding Information: We thank R. Bosselut (National Cancer Institute of the US National Institutes of Health) for mice expressing the transgene encoding Th-POK; S.-C. Bae (Chungbuh National University) for the Myc-tagged Runx3 expression plasmid; B.J. Fowlkes for input and discussions; Y. Wakabayashi and Y. Luo (NHLBI) for high-throughput sequencing and data processing; T. Zhao for animal husbandry; the Flow Cytometry Core facility at the University of Iowa (J. Fishbaugh, H. Vignes and G. Rasmussen) for support for cell sorting; and Radiation Core facility at the University of Iowa (A. Kalen) for mouse irradiation. Supported by the American Cancer Society (RSG-11-161-01-MPC to H.-H.X.) and the US National Institutes of Health (HL095540 and AI105351 to H.-H.X.; HG006130 to K.T.; AI007485 (for support of F.C.S.); and P30CA086862 and 1S10 RR027219 to the Flow Core Facility at the University of Iowa). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health.",
year = "2014",
month = jul,
doi = "10.1038/ni.2897",
language = "English",
volume = "15",
pages = "646--656",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Research",
number = "7",
}