Abstract
Activated by AMP-dependent and -independent mechanisms, AMP-activated protein kinase (AMPK) plays a central role in the regulation of cellular bioenergetics and cellular survival. AMPK regulates a diverse set of signaling networks that converge to epigenetically mediate transcriptional events. Reversible histone and DNA modifications, such as acetylation and methylation, result in structural chromatin alterations that influence transcriptional machinery access to genomic regulatory elements. The orchestration of these epigenetic events differentiates physiological from pathophysiological phenotypes. AMPK phosphorylation of histones, DNA methyltransferases and histone post-translational modifiers establish AMPK as a key player in epigenetic regulation. This review focuses on the role of AMPK as a mediator of cellular survival through its regulation of chromatin remodeling and the implications this has for health and disease.
Highlights
Epigenetic regulation gives rise to a spectrum of cellular phenotypes observed in a single organism independent of primary DNA sequence
Such adaptation for survival early in life initiates epigenetic programming that correlates with AMPK activation and determines predisposition to disease
AMPK, both directly and indirectly, regulates the post-translational modification (PTM) status of histones that play a major role in the regulation of nucleosome structure
Summary
Epigenetic regulation gives rise to a spectrum of cellular phenotypes observed in a single organism independent of primary DNA sequence. Influencing gene expression, epigenetics promotes organismal adaption by offering substantial functional variability in response to environmental stimuli [1,2,3] This regulation occurs, in part, through nucleosomal remodeling as a result of histone, DNA, and DNA-binding protein modifications that include: phosphorylation, acetylation, O-GlcNAcylation, ribosylation, and methylation. Chronic AMPK activation plays a role in cellular and organismal inheritance, evidenced by its multi-isoform 2R-ohnologue characteristics, which are often evolutionarily conserved in gene coding regions to support basic survival functions and to increase the possibility for complex tissue diversity and adaptation [15,16,17] Such adaptation for survival early in life initiates epigenetic programming that correlates with AMPK activation and determines predisposition to disease. The mechanistic basis for this regulation, as well as its implications for inheritance, is still under exploration, these collective observations point to a fundamentally important role of AMPK as an epigenetic regulator
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