TGF-beta1-induced myofibroblast activation (increased SMA expression) (p<0.001 vs control) was accompanied by a net decrease in total H3 acetylation (p<0.001 vs control), although changes in individual marks were variable. This was paralleled by a generalised reduction in histone acetyltransferases (HAT), and divergent changes in histone deacetylase (HDAC) enzymes at both transcript and protein levels. Globally this was manifest in a reduction in total HAT activity (p<0.001) and increase in HDAC activity (p<0.01). TGF-beta1 induced a shift in cellular metabolism from oxidative respiration to aerobic glycolysis resulting in reduced acetyl-CoA. The reduction in total H3 acetylation could be rescued by providing exogenous citrate (p=ns vs control), a source of acetyl-CoA, without ameliorating changes in HAT/ HDAC activity. Conclusions: TGF-beta1 produces a metabolic reprogramming in renal fibroblasts, with less H3 acetylation through reduced acetyltransferase activity, increased deacetylation and changes in carbon availability. Our results suggest that acetyl-CoA availability predominates over HAT and HDAC activity as a key determinant of H3 acetylation in response to TGF-beta1
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