Table 1.
Biochemical measurements of interactions between epigenetic modifiers and regulatory metabolites. Metabolic sensitivity indicates evidence for regulatory metabolites promoting or impeding chromatin modification in cells (y = yes, n = no, nd = not determined). References for data: Gcn5,148 p300,149, 150 pCAF,151 KDM4A/KDM4C,46 PHD2,31, 46, 48 EZH1/EZH2,152 CARM1,152, 153 SIRT1,154 CtBp.155 Gcn5 values from yeast homologue, Kd for CoA obtained with etheno-CoA; p300 Ac-CoA and CoA Kd and Ki obtained with acetonyl-CoA and desulfo-CoA respectively; SIRT1 Ki value from yeast homologue (Sir2). All values are given without standard deviations and have been rounded to the nearest decimal for simplicity.
| Epigenetic modifier | Regulatory metabolite | Km (μM) | Kd (μM) | IC50 or Ki (μM) | Chromatin mark | Metabolic sensitivity |
|---|---|---|---|---|---|---|
| Gcn5 | Ac-CoA | 2.5 | 8.5 | - | H3K14Ac | y |
| CoA | - | 5.1 | 6.7 | |||
| p300 | Ac-CoA | 1.2 | 0.7 | - | H3/H4Ac | nd |
| CoA | - | 7.3 | 8.1 | |||
| Pcaf | Ac-CoA | 1 | 0.6 | - | H3K9Ac | nd |
| CoA | - | - | 0.4 | |||
| KDM4A | a-KG | 6 | - | - | H3K9me3 (removal) | y |
| R-2-HG | - | - | 24 | |||
| KDM4C | a-KG | 4 | - | - | H3K9me3 (removal) | y |
| R-2-HG | - | - | 79 | |||
| PHD2 | a-KG | 1 | - | - | HIF-1 genomic occupancy reduced | y |
| R-2-HG | 210 | - | 7300 | |||
| succinate | - | - | 350 | |||
| fumarate | - | - | 80 | |||
| EZH1 | SAM | 2.5 | - | - | H3K27me | y |
| SAH | - | - | 8.3 | (me2/me3) | ||
| EZH2 | SAM | 1.2 | - | - | H3K27me | y |
| SAH | - | - | 7.5 | (me2/me3) | ||
| CARM1 | SAM | 0.2 | 0.8 | - | H3R17me2a | n |
| SAH | - | 6.9 | 0.1 | |||
| SIRT1 | NAD+ | 154 | - | - | H3K9Ac (removal) | y |
| NADH | - | - | 28000 | |||
| CtBP | NAD+ | - | 11 | - | co-repressor | y |
| NADH | - | 0.07 | - |