Abstract IA12: Dynamic metabolic regulation of epigenetic remodeling in macrophages

Over the course of an immune response, macrophages undergo a sequence of functional transitions. These transitions are coupled to dynamic rewiring of cellular metabolism. The impact of metabolic state on chromatin modifications allows the dynamic metabolic reprogramming to orchestrate immunity during immune responses. Specifically, we found that in response to the classic stimuli lipopolysaccharide and interferon-γ, pyruvate dehydrogenase complex is profoundly inhibited over time, mediating the metabolic transition from the early pro-inflammatory stage to the later more immunosuppressive stage. The regulation of PDHC activity dynamically controls cellular acetyl-coA availability. We will discuss how this affects histone acetylation in macrophages over a course of prolonged stimulation and upon repeated stimulation. Furthermore, our study revealed that several metabolites directly involved in the addition or removal of histone methylation, such as S-adenosyl-methionine and succinate, show highly dynamic changes during the immune response. We will discuss which specific epigenetic modifications are sensitive to fluctuations in metabolite levels. This work reveals important mechanisms connecting metabolism, epigenetic and changes in macrophage functions during immune response. Citation Format: Jing Fan. Dynamic metabolic regulation of epigenetic remodeling in macrophages [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA12.