title: The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes.
abstract: 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.
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Matthias
authors.initials: M
authors.lastname: Hombauer
authors.forename: Ivan
authors.initials: I
authors.lastname: Bilic
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Naoe
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schebesta
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
authors.forename: Wilfried
authors.initials: W
authors.lastname: Ellmeier
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D054338:Cell Transdifferentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D053263:Gene Regulatory Networks; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism; D038041:Lymphopoiesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011828:Radiation Chimera; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D037941:Silencer Elements, Transcriptional / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D006183:H-2 Antigens; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins; D014157:Transcription Factors; C497211:Zbtb7b protein, mouse; C485875:Zfp278 protein, mouse
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