title: Yin Yang 1 Promotes Thymocyte Survival by Downregulating p53.
abstract: Yin Yang 1 (YY1) is a zinc finger protein that functions as a transcriptional activator or repressor and participates in multiple biological processes, including development and tumorigenesis. To investigate the role of YY1 in developing T cells, we used mouse models that depleted YY1 at two distinct stages of thymocyte development. When YY1 was depleted in CD4(-)CD8(-) double-negative thymocytes, development to the CD4(+)CD8(+) double-positive stage was impaired, due to increased apoptosis that prevented expansion of post-β-selection thymocytes. When YY1 was depleted in double-positive thymocytes, they underwent increased cell-autonomous apoptosis in vitro and displayed a shorter lifespan in vivo, as judged by their ability to undergo secondary Vα-to-Jα recombination. Mechanistically, we found that the increased apoptosis in YY1-deficient thymocytes was attributed to overexpression of p53, because concurrent loss of p53 completely rescued the developmental defects of YY1-deficient thymocytes. These results indicated that YY1 functions as a critical regulator of thymocyte survival and that it does so by suppressing the expression of p53.
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
authors: Liang
authors: http://orcid.org/0000-0002-0440-0306
authors: L
authors: Chen
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
authors: Daniel P
authors: http://orcid.org/0000-0001-6114-9237
authors: DP
authors: Foreman
authors: Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901.
authors: Derek B
authors: http://orcid.org/0000-0002-5510-9367
authors: DB
authors: Sant'Angelo
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and krang001@mc.duke.edu.
authors: Michael S
authors: http://orcid.org/0000-0003-1292-254X
authors: MS
authors: Krangel
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D002470:Cell Survival / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D060168:Thymocytes / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000276:immunology; D050986:YY1 Transcription Factor / Q000276:immunology*
chemical_list: D016159:Tumor Suppressor Protein p53; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse