The CD4 versus CD8 lineage specification of thymocytes is linked to coreceptor expression. The transcription factor MAZR has been identified as an important regulator of Cd8 expression. Here we show that variegated CD8 expression by loss of Cd8 enhancers was reverted in MAZR-deficient mice, which confirms that MAZR negatively regulates the Cd8 loci during the transition to the double-positive (DP) stage. Moreover, loss of MAZR led to partial redirection of major histocompatibility complex (MHC) class I–restricted thymocytes into CD4+ helper-like T cells, which correlated with derepression of Th-POK, a central transcription factor for helper-lineage development. MAZR bound the silencer of the gene encoding Th-POK, which indicated direct regulation of this locus by MAZR. Thus, MAZR is part of the transcription factor network that regulates the CD8 lineage differentiation of DP thymocytes.
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We thank M. Sibilia (Medical University of Vienna) for OT-I TCR-transgenic mice; D. Stoiber-Sakaguchi (Medical University of Vienna) for OT-II TCR-transgenic mice; W. Held (Glaxo) for recombinant human interleukin 2; J. Kaye for information about primer sequences that detect Tox expression; M. Willheim and G. Hofbauer for cell sorting; H. Tanaka for technical advice; E. Pfeiffer for help with irradiation; M. Busslinger for help with some animal experiments; D. Stoiber-Sakaguchi, J. Raberger and N. Boucheron for critical reading of the manuscript; and the National Institutes of Health Tetramer facility for CD1d reagents with and without PBS57. Supported by the Austrian Science Fund (P16708 and P19930), the START Program of the Austrian Ministry of Science and Research (project Y-163), the RIKEN Research Center for Allergy and Immunology (International Collaboration Program) and the Ernst Schering Foundation (M.H.).
The authors declare no competing financial interests.
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Sakaguchi, S., Hombauer, M., Bilic, I. et al. The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes. Nat Immunol 11, 442–448 (2010). https://doi.org/10.1038/ni.1860
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