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 effic...

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Bibliographic Details
Published in:The Journal of experimental medicine 2010-05, Vol.207 (5), p.915-922
Main Authors: Lehnertz, Bernhard, Northrop, Jeffrey P, Antignano, Frann, Burrows, Kyle, Hadidi, Sima, Mullaly, Sarah C, Rossi, Fabio M V, Zaph, Colby
Format: Article
Language:English
Subjects:
Adult
Animals
Brief Definitive Report
CD4-Positive T-Lymphocytes - enzymology
CD4-Positive T-Lymphocytes - immunology
Cell Differentiation
Embryonic Development
Gene Expression Regulation, Enzymologic
Gene Silencing
Histocompatibility Antigens - genetics
Histocompatibility Antigens - metabolism
Histone-Lysine N-Methyltransferase - deficiency
Histone-Lysine N-Methyltransferase - genetics
Histone-Lysine N-Methyltransferase - metabolism
Humans
Interferon-gamma - genetics
Interleukin-17 - genetics
Mice
Mice, Transgenic
Polymerase Chain Reaction
RNA, Messenger - genetics
Stem Cells - cytology
T-Lymphocytes - cytology
T-Lymphocytes - enzymology
T-Lymphocytes - immunology
T-Lymphocytes, Helper-Inducer - cytology
T-Lymphocytes, Helper-Inducer - enzymology
T-Lymphocytes, Helper-Inducer - immunology
Trichuriasis - immunology
Trichuriasis - prevention & control
Trichuris
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Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20100363