Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes dep...Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes depend on many co-substrates and cofactors,such as 2-oxoglutarate(2-OG),iron,S-adenosylmethionine(SAM),nicotinamide adenine dinucleotide(NAD+),flavin adenine dinucleotide(FAD),and acetyl-CoA.These factors are inter-connecting molecules that integrate cellular nutrient metabolism and redox homeostasis,two key regulators of cell proliferation,cell survival,and cell functions.Dysregulation of such delicate regulatory network has been implicated in many pathological conditions and also been increasingly recognized as an emerging mechanism responsible for environmental pollutant-induced adverse effects.In this review,we first summarize DNA and histone modifying enzymes and their essential factors,then discuss the metabolic sources and the redox regulatory roles of these enzymatic factors,and finally elaborate the mechanisms of how targeting such factors by environmental pollutants influences epigenetic regulation and perturbs cellular functions.展开更多
基金This work is funded by National Natural Science Foundation of China(No.81773466)to W.H,and by Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease(No.DXWL2023-06)to W.X.
文摘Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes depend on many co-substrates and cofactors,such as 2-oxoglutarate(2-OG),iron,S-adenosylmethionine(SAM),nicotinamide adenine dinucleotide(NAD+),flavin adenine dinucleotide(FAD),and acetyl-CoA.These factors are inter-connecting molecules that integrate cellular nutrient metabolism and redox homeostasis,two key regulators of cell proliferation,cell survival,and cell functions.Dysregulation of such delicate regulatory network has been implicated in many pathological conditions and also been increasingly recognized as an emerging mechanism responsible for environmental pollutant-induced adverse effects.In this review,we first summarize DNA and histone modifying enzymes and their essential factors,then discuss the metabolic sources and the redox regulatory roles of these enzymatic factors,and finally elaborate the mechanisms of how targeting such factors by environmental pollutants influences epigenetic regulation and perturbs cellular functions.
