Activating and inhibitory functions for the histone lysine methyltransferase G9a in T helper cell differentiation and function.
Accumulating evidence suggests that the regulation of gene expression by histone lysine methylation is crucial for several biological processes. The histone lysine methyltransferase G9a is responsible for the majority of dimethylation of histone H3 at lysine 9 (H3K9me2) and is required for the efficient repression of developmentally regulated genes during embryonic stem cell differentiation. However, whether G9a plays a similar role in adult cells is still unclear. We identify a critical role for G9a in CD4(+) T helper (Th) cell differentiation and function. G9a-deficient Th cells are specifically impaired in their induction of Th2 lineage-specific cytokines IL-4, IL-5, and IL-13 and fail to protect against infection with the intestinal helminth Trichuris muris. Furthermore, G9a-deficient Th cells are characterised by the increased expression of IL-17A, which is associated with a loss of H3K9me2 at the Il17a locus. Collectively, our results establish unpredicted and complex roles for G9a in regulating gene expression during lineage commitment in adult CD4(+) T cells.
Lehnertz
Bernhard
B
The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Northrop
Jeffrey P
JP
Antignano
Frann
F
Burrows
Kyle
K
Hadidi
Sima
S
Mullaly
Sarah C
SC
Rossi
Fabio M V
FM
Zaph
Colby
C
D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D002454:Cell Differentiation; D047108:Embryonic Development; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D014257:Trichuriasis / Q000276:immunology / Q000517:prevention & control; D014258:Trichuris
D006649:Histocompatibility Antigens; D020381:Interleukin-17; D012333:RNA, Messenger; D007371:Interferon-gamma; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase