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

• Published in: The Journal of immunology (1950) Vol. 200; no. 12; pp. 3891 - 3896
• Main Authors: Verbaro, Daniel J, Sakurai, Nagisa, Kim, Byungil, Shinkai, Yoichi, Egawa, Takeshi
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 15-06-2018
• 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1701700

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.