G9a regulates group 2 innate lymphoid cell development by repressing the group 3 innate lymphoid cell program.
- Abstract:
- 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.
- Authors:
- F Antignano, M Braam, MR Hughes, AL Chenery, K Burrows, MJ Gold, MJ Oudhoff, D Rattray, TY Halim, A Cait, F Takei, FM Rossi, KM McNagny, C Zaph
- Journal:
- J Exp Med
- Citation info:
- 213(7):1153-1162
- Publication date:
- 27th Jun 2016
- Full text
- DOI