Cutting Edge: The Histone Methyltransferase G9a Is Required for Silencing of Helper T Lineage-Associated Genes in Proliferating CD8 T Cells

Helper versus cytotoxic T lineage decision in the thymus has been studied as a model for silencing of alternative lineage genes. Although the transcription factor RUNX3 is required for the initiation of silencing in developing CD8 T cells, it is unknown how silencing of and other helper T lineage ge...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2018-06, Vol.200 (12), p.3891-3896
Main Authors: Verbaro, Daniel J, Sakurai, Nagisa, Kim, Byungil, Shinkai, Yoichi, Egawa, Takeshi
Format: Article
Language:English
Subjects:
Animals
CD4 antigen
CD4 Antigens - genetics
CD8 antigen
CD8-Positive T-Lymphocytes - metabolism
Cell division
Cell Lineage - genetics
Cell Proliferation - genetics
Core Binding Factor Alpha 3 Subunit - genetics
Cytotoxicity
Down-Regulation - genetics
Gene silencing
Gene Silencing - physiology
Histone methyltransferase
Histone-Lysine N-Methyltransferase - metabolism
Inflammation
Listeria
Listeria monocytogenes
Listeria monocytogenes - metabolism
Lymphocyte Activation - genetics
Lymphocytes
Lymphocytes T
Lymphopenia
Lymphopenia - genetics
Lymphopenia - metabolism
Mice
Mice, Inbred C57BL
Runx3 protein
T-Lymphocytes, Helper-Inducer - metabolism
Thymus
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Summary:Helper versus cytotoxic T lineage decision in the thymus has been studied as a model for silencing of alternative lineage genes. Although the transcription factor RUNX3 is required for the initiation of silencing in developing CD8 T cells, it is unknown how silencing of and other helper T lineage genes is maintained. We show that the histone methyltransferase G9a is necessary for silencing helper T lineage genes in proliferating mouse CD8 T cells. Despite normal initial downregulation, G9a-deficient CD8 T cells derepress and other helper lineage genes during repeated division in lymphopenia or in response to tumor Ag. However, G9a was dispensable for continued silencing of those genes in CD8 T cells that respond to infection by These results demonstrate that G9a facilitates maintenance of cellular identity of CD8 T cells during cell division, which is further reinforced by inflammatory signals.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1701700