Alum Speaker

The Metabolic Regulation of Epigenetic Phenomena Or: Why Everyone Needs to Know the Krebs Cycle

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Abstract

Epigenetic phenomena encompass a broad spectrum of post-translational modifications to nuclear proteins as well as chemical modifications of the DNA bases themselves. Increasingly, researchers are identifying linkages between central metabolic pathways and the epigenetic regulation of gene expression through intermediates such as succinate and 2-oxoglutarate. Fluctuations in these intermediates caused by both physiologic and pathologic stimuli leads to demonstrable changes in epigenetic marks in the nucleus, which in turn can alter gene expression. This process may play an important role in the development of cancer, among other human diseases. In this presentation, a brief overview of epigenetic regulation, the enzymes responsible, and their linkages with central metabolism will be introduced. The presentation will close with a series of examples relevant to human disease, including the role of succinate dehydrogenase and isocitrate dehydrogenase as relatively novel tumor suppressors.