MAZR and Runx Factors Synergistically Repress ThPOK during CD8+ T Cell Lineage Development.
J Immunol
; 195(6): 2879-87, 2015 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-26254341
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 ß (CBFß) 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Factores de Transcripción
/
Linfocitos T CD8-positivos
/
Subunidad alfa 2 del Factor de Unión al Sitio Principal
/
Subunidad alfa 3 del Factor de Unión al Sitio Principal
/
Proteínas de Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2015
Tipo del documento:
Article