Metabolism and epigenetics

Almost all cells that constitute an organism contain nearly identical genomic DNA. However, cellular identities differ greatly according to their function. This plethora of cellular phenotypes is owed to the distinct gene expression dictated by the epigenome. The epigenome encompasses genetic modifications that do not change the underlying genetic code. These modifications manifest themselves as DNA methylation or the post-translational modification of histones. Thus far, numerous histone modifications have been reported, including methylation, acetylation, phosphorylation, lactylation, acylation, hydroxylation, ubiquitylation, glycation, serotonylation, glycosylation, sumoylation and ADP-ribosylation. There is a close link between epigenetic modifications and cellular metabolism: nutrient derived metabolites serve as substrates and cofactors in remodelling the epigenetic landscape. For instance, the availability of α-Ketoglutarate as a cofactor for histone demethylases dictates fundamental biological processes like embryonic development. However, the underlying molecular mechanisms that connect the α-Ketoglutarate metabolism with epigenetic gene regulation remains elusive. Our research strives to understand how metabolic and epigenetic enzymes work in concert to orchestrate epigenetic gene regulation.