Fig. 3: Fatty acid oxidation supports ACLY-mediated histone acetylation.
a, The percentage of 13C-labeled H3K27ac in 13C-labeled BMDMs pulsed with palmitic acid stimulated with or without FGK45 mAb was determined by proteomics. The basal labeling level of 13C-labeled H3K27ac (dashed line) was determined by the same approach in BMDMs treated with ACLY inhibitor. b, qPCR analysis of mRNA expression of pro-inflammatory marker genes in BMDMs cells stimulated with or without FGK45 mAb in the absence or presence of C646, p300/HAT inhibitor, under glucose-deplete media. c, Representative immunoblots of indicated proteins in lysates of Cas9-expressing BMDMs harboring control sgRNA (Ctrl) and ACLY gRNAs (ACLY sgRNA-1 and sgRNA-2) stimulated with or without FGK45 mAb under glucose-deplete media. d, qPCR analysis of mRNA expression of mRNA expression of pro-inflammatory marker genes in Cas9-expressing BMDMs harboring control sgRNA (Ctrl) and ACLY gRNAs (ACLY sgRNA-1 and sgRNA-2) stimulated with or without FGK45 mAb under glucose-deplete media. e,f, Tumor growth (e) and tumor weight (f) in tumor-bearing mice transplanted with either indicated bone marrows and then treated with either PBS or FGK45 mAb. g, Relative fold change in mRNA expression of pro-inflammatory marker genes in TAMs isolated from tumor-bearing mice transplanted with either indicated bone marrows and then treated with either PBS or FGK45 mAb. In a, representative data or pooled data from two individual experiments with n = 3 per group. In b–d, data are representative of three individual experiments with n = 3 per group. e–g, Representative data or pooled data from two individual experiments with n = 4 mice per group in e; n = 7 for Ctrl-PBS, n = 5 for Ctrl-FGK45, n = 8 for ACLY gRNA-PBS and n = 7 for ACLY gRNA-FGK45 in f and n = 8 in g. All data are the mean ± s.d. and analyzed by a two-tailed Student’s t-test.
