title: MAZR and Runx Factors Synergistically Repress ThPOK during CD8+ T Cell Lineage Development.
abstract: Th-inducing Pox virus and zinc finger/Krüppel-like factor (ThPOK) is a key commitment factor for CD4(+) lineage T cells and is essential for the maintenance of CD4 lineage integrity; thus, the expression of ThPOK has to be tightly controlled. In this article, we demonstrate that Myc-associated zinc finger-related factor (MAZR) and Runt-related transcription factor 1 (Runx1) together repressed ThPOK in preselection double-positive thymocytes, whereas MAZR acted in synergy with Runx3 in the repression of ThPOK in CD8(+) T cells. Furthermore, MAZR-Runx1 and MAZR-Runx3 double-mutant mice showed enhanced derepression of Cd4 in double-negative thymocytes and in CD8(+) T cells in comparison with Runx1 or Runx3 single-deficient mice, respectively, indicating that MAZR modulates Cd4 silencing. Thus, our data demonstrate developmental stage-specific synergistic activities between MAZR and Runx/core-binding factor β (CBFβ) complexes. Finally, retroviral Cre-mediated conditional deletion of MAZR in peripheral CD8(+) T cells led to the derepression of ThPOK, thus showing that MAZR is also part of the molecular machinery that maintains a repressed state of ThPOK in CD8(+) T cells.
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; shinya.sakaguchi@meduniwien.ac.at wilfried.ellmeier@meduniwien.ac.at.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sakaguchi
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
authors.forename: Daniela
authors.initials: D
authors.lastname: Hainberger
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
authors.forename: Caroline
authors.initials: C
authors.lastname: Tizian
authors.affiliation: Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; and.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Prefectural University of Medicine Kyoto, Kyoto 602-8566, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Okuda
authors.affiliation: Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; and.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; shinya.sakaguchi@meduniwien.ac.at wilfried.ellmeier@meduniwien.ac.at.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Ellmeier
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage / Q000276:immunology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000276:immunology*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000276:immunology*; D050660:Core Binding Factors / Q000276:immunology; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050660:Core Binding Factors; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C493726:Runx1 protein, mouse; C493730:Runx3 protein, mouse; C497211:Zbtb7b protein, mouse; C485875:Zfp278 protein, mouse