G9a regulates group 2 innate lymphoid cell development by repressing the group 3 innate lymphoid cell program
| Autor: | Mitchell J.S. Braam, Alissa Cait, Matthew J. Gold, Timotheus Y.F. Halim, Michael R. Hughes, Menno J. Oudhoff, Fumio Takei, Kyle Burrows, Kelly M. McNagny, David G Rattray, Alistair Chenery, Fabio M.V. Rossi, Frann Antignano, Colby Zaph |
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| Přispěvatelé: | Antignano, Frann [0000-0003-0502-5330], Braam, Mitchell [0000-0002-3038-5859], Hughes, Michael R [0000-0002-7925-6070], Oudhoff, Menno J [0000-0002-1180-8975], Rattray, David [0000-0002-2444-0663], Halim, Timotheus Y [0000-0001-9773-0023], Takei, Fumio [0000-0002-3620-5046], McNagny, Kelly M [0000-0003-4737-3499], Zaph, Colby [0000-0002-9889-9848], Apollo - University of Cambridge Repository |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Methyltransferase Immunology Epigenesis Genetic Histones Mice 03 medical and health sciences 0302 clinical medicine Immune system Animals Immunology and Allergy Gene silencing Lymphocytes Epigenetics Gene Psychological repression Research Articles Mice Knockout biology Innate lymphoid cell Brief Definitive Report Histone-Lysine N-Methyltransferase Hematopoietic Stem Cells Immunity Innate 3. Good health Cell biology 030104 developmental biology Histone biology.protein Gene Deletion 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20151646 |
| Popis: | Antignano, Zaph, and collaborators show that the lysine methyltransferase G9a plays a critical role in determining the developmental programs of group 2 and 3 innate lymphoid cells. Innate lymphoid cells (ILCs) are emerging as important regulators of homeostatic and disease-associated immune processes. Despite recent advances in defining the molecular pathways that control development and function of ILCs, the epigenetic mechanisms that regulate ILC biology are unknown. Here, we identify a role for the lysine methyltransferase G9a in regulating ILC2 development and function. Mice with a hematopoietic cell–specific deletion of G9a (Vav.G9a−/− mice) have a severe reduction in ILC2s in peripheral sites, associated with impaired development of immature ILC2s in the bone marrow. Accordingly, Vav.G9a−/− mice are resistant to the development of allergic lung inflammation. G9a-dependent dimethylation of histone 3 lysine 9 (H3K9me2) is a repressive histone mark that is associated with gene silencing. Genome-wide expression analysis demonstrated that the absence of G9a led to increased expression of ILC3-associated genes in developing ILC2 populations. Further, we found high levels of G9a-dependent H3K9me2 at ILC3-specific genetic loci, demonstrating that G9a-mediated repression of ILC3-associated genes is critical for the optimal development of ILC2s. Together, these results provide the first identification of an epigenetic regulatory mechanism in ILC development and function. |
| Databáze: | OpenAIRE |
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