Epigenetic Regulation by Metabolic Intermediates

The interplay between cellular metabolism and epigenetics has emerged as a major frontier in biomedical research, revealing that metabolic intermediates do far more than support cellular energetics and biosynthesis: they also act as direct regulators of chromatin organization and gene expression. A growing body of work has shown that metabolites such as acetyl-CoA, S-adenosylmethionine, α-ketoglutarate, succinate, fumarate, lactate, and NAD+ can modulate the activity of epigenetic enzymes, thereby influencing DNA methylation, histone modifications, chromatin accessibility, and transcriptional programs. Despite these advances, important questions remain regarding how fluctuations in metabolite abundance, localization, and flux are sensed and translated by the epigenetic machinery, and how these processes shape cellular identity, adaptation, and dysfunction in different physiological and pathological contexts.This Research Topic aims to advance our understanding of how metabolic intermediates regulate epigenetic states and chromatin-based processes across diverse biological systems. We seek contributions that clarify the molecular mechanisms linking metabolism to chromatin remodeling and gene regulation, and that illuminate how these interactions influence transcription, development, differentiation, stress responses, and disease progression. By integrating molecular, cellular, and systems-level perspectives, this collection will provide a broader framework for understanding the metabolism–epigenome interface and its relevance to both fundamental biology and translational research.The scope of this Research Topic includes both basic and applied studies addressing metabolite-driven epigenetic regulation in normal physiology and disease. Studies in development, stem cell biology, cancer, aging, immunity, and metabolic, cardiovascular, and neurological disorders are particularly welcome. We encourage submissions that address, but are not limited to, the following themes:• Molecular roles of metabolic intermediates and cofactors in regulating epigenetic enzymes• Acetyl-CoA, NAD+, SAM, α-ketoglutarate, succinate, fumarate, lactate, and related metabolites in chromatin regulation• Metabolic control of DNA methylation, histone methylation, acetylation, and demethylation• Effects of metabolite availability, compartmentalization, and flux on epigenetic remodeling• Interplay between mitochondrial function, central carbon metabolism, and chromatin state• Metabolite-dependent transcriptional reprogramming during development, differentiation, and cellular stress• Epigenetic consequences of metabolic rewiring in disease pathogenesis• Therapeutic strategies targeting metabolism–epigenome interactionsWe welcome original research articles, reviews, mini-reviews, methods, and perspectives that address these and related topics Topic editors: Kyunghwan Kim, Jean-Pierre Etchegaray Source: https://www.frontiersin.org/research-topics/77314/epigenetic-regulation-by-metabolic-intermediates