title: Activating and inhibitory functions for the histone lysine methyltransferase G9a in T helper cell differentiation and function.
abstract: 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.
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lehnertz
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Northrop
authors.forename: Frann
authors.initials: F
authors.lastname: Antignano
authors.forename: Kyle
authors.initials: K
authors.lastname: Burrows
authors.forename: Sima
authors.initials: S
authors.lastname: Hadidi
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Mullaly
authors.forename: Fabio M V
authors.initials: FM
authors.lastname: Rossi
authors.forename: Colby
authors.initials: C
authors.lastname: Zaph
mesh_terms: 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
chemical_list: D006649:Histocompatibility Antigens; D020381:Interleukin-17; D012333:RNA, Messenger; D007371:Interferon-gamma; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase