Yin Yang 1 promotes thymocyte survival by downregulating p53

Liang Chen, Daniel P. Foreman, Derek Sant'Angelo, Michael S. Krangel

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 cellautonomous 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.

Original languageEnglish (US)
Pages (from-to)2572-2582
Number of pages11
JournalJournal of Immunology
Volume196
Issue number6
DOIs
StatePublished - Mar 15 2016

Fingerprint

Yin-Yang
Thymocytes
Down-Regulation
Apoptosis
Biological Phenomena
Zinc Fingers
Genetic Recombination
Carcinogenesis
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Chen, Liang ; Foreman, Daniel P. ; Sant'Angelo, Derek ; Krangel, Michael S. / Yin Yang 1 promotes thymocyte survival by downregulating p53. In: Journal of Immunology. 2016 ; Vol. 196, No. 6. pp. 2572-2582.
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Yin Yang 1 promotes thymocyte survival by downregulating p53. / Chen, Liang; Foreman, Daniel P.; Sant'Angelo, Derek; Krangel, Michael S.

In: Journal of Immunology, Vol. 196, No. 6, 15.03.2016, p. 2572-2582.

Research output: Contribution to journalArticle

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AB - 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 cellautonomous 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.

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