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Status |
Public on May 11, 2018 |
Title |
Ezh2 is essential for activation-induced CD8+ T cell cycle progression via repressing Cdkn1a and Cdkn2c expression (Part II) |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Transition from resting to cell cycle in response to antigenic stimulation is an essential step for naïve CD8+ T cells to differentiate to effector and memory cells. Leaving the resting state requires dramatic changes of chromatin status in the key cell cycle inhibitors but the details of these concerted events are not fully elucidated. Here, we showed that Ehz2, an enzymatic component of polycomb repressive complex 2 (PRC2) catalyzing the trimethylation of lysine 27 on histone 3 (H3K27me3), regulates activation induced naïve CD8+ T cells proliferation and apoptosis. When Ezh2 was deleted during thymocyte development (Ezh2fl/flCD4Cre+ mice), naive CD8+ T cells displayed impaired proliferation and increased apoptosis in response to antigen stimulation. However, naive CD8+ T cells only had impaired proliferation but no increased apoptosis when Ezh2 was deleted after activation (Ezh2fl/flGzmBCre+ mice), suggesting cell cycle and apoptosis are temporally separable events controlled by Ezh2. We then showed that deletion of Ezh2 resulted in the increased expression of cyclin-dependent kinase inhibitors Cdkn2a (p16 and Arf) and Cdkn1c (p57) in activated naïve CD8+ T cells as the consequence of reduced levels of H3K27me3 in these two gene loci. Finally, with real time imaging, we observed prolonged cell division times of naïve CD8+ T cells in the absence of Ezh2 post in vitro stimulation. Together, these findings reveal that repression of Cdkn2a and Cdkn1c by Ezh2 plays an essential role in permission of activation-induced CD8+ T cell proliferation.
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Overall design |
To understand how Ezh2, an enzymatic component of polycomb repressive complex 2 (PRC2) catalyzing the trimethylation of lysine 27 on histone 3 (H3K27me3), regulates activation induced naïve CD8+ T cells proliferation and apoptosis. We used Ezh2fl/flCD4Cre+ mice to analyze naive CD8+ T cells proliferation and function during immune response. We analyzed cell cycle progression, apoptosis, global gene expression, and histone H3K27me3 in specific cell cycle regulators in naive CD8 T cells .
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Contributor(s) |
Chen G, Weng N |
Citation(s) |
29632530 |
Submission date |
Nov 02, 2017 |
Last update date |
May 11, 2018 |
Contact name |
Minoru S.H. Ko |
E-mail(s) |
kom@mail.nih.gov
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Phone |
410-558-8359
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Organization name |
NIH
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Department |
National Institute on Aging
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Lab |
Lab of Genetics
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Street address |
251 Bayview Blvd, Suite 100, 10C
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City |
Baltimore |
State/province |
MD |
ZIP/Postal code |
21224 |
Country |
USA |
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Platforms (1) |
GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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Samples (10)
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This SubSeries is part of SuperSeries: |
GSE106426 |
Ezh2 is essential for activation-induced CD8+ T cell cycle progression via repressing Cdkn1a and Cdkn2c expression |
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Relations |
BioProject |
PRJNA416855 |