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. 2021 Apr 30;7(18):eabe7359. doi: 10.1126/sciadv.abe7359

Fig. 8. Mitochondrial respiration is required for epigenetic regulation of Vegfr3 and Prox1.

Fig. 8

Mitochondrial complex III inhibition with antimycin A alters TCA cycle metabolites (A) and 2HG levels (B). Values are normalized to mean of control group. (C) ChIP-seq analysis of H3K27ac, H3K4me3, and H3K4me1 histone modifications in LEC cultures treated with vehicle control (Ctrl) or antimycin A (Anti) for 48 hours. Track examples for LEC-specific genes (Prox1 and Vegfr3) and BEC genes (Nrp1 and ICAM1) are shown. Antimycin A–treated LECs show a marked reduction in the H3K4me3 and H3K27ac signal at the Vegfr3 locus and a reduction in H3K4me3 in the Prox1 locus, while H3K27ac peaks are increased in the Nrp1 and ICAM1 locus. (D) ChIP-seq analysis of the same modifications in (C) in LECs and BECs reveals that H3K27ac and H3K4me3 peaks are elevated in the Prox1 and Vegfr3 loci in LECs, whereas those of Nrp1 and ICAM1 are reduced in LECs and BECs. Scale bar, 5 kb. Each data point represents a biological replicate. All results are presented as means ± SEM and analyzed by multiple t test or two-tailed Student’s t test.