Metabolism shaping chromatin shaping metabolism
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Cellular and Molecular Life Sciences
MULTI-AUTHOR REVIEW
Metabolism shaping chromatin shaping metabolism J. Andrew Pospisilik
Received: 29 January 2013 / Revised: 5 February 2013 / Accepted: 5 February 2013 / Published online: 9 March 2013 © Springer Basel 2013
Keywords Metabolism · Epigenetics · Developmental reprogramming · Chromatin · Diabetes · Obesity
Overall, our understanding of biology develops slowly, bursting forward intermittently on the heels of stochastic conceptual breakthroughs. Indeed, the seed for one such surge was laid recently: the last decades have seen the identification of multiple epigenetic regulatory niveaus, previously underappreciated systems that govern virtually all genetically determined biological processes. Crudely, these systems can be said to include all chromatin-based biology contributing towards maintenance of phenotype through cell division. They are numerous and are founded upon stable molecular signatures that can be written, read, erased, and maintained, and, critically, that contribute directly towards the establishment of diverse functional states. These “chromatin states”, which code for such basic functions as active or silenced transcription and housekeeping, are fundamental to cellular identity. Their disruption can lead to a variety of changes, from subtle to catastrophic, depending on the cell type and system. They can induce acquisition and loss of stemness, initiate and exacerbate cancer, and they are capable of disrupting virtually all genetically coded cell-specific functional repertoires, from simple cellular metabolism to the complexities of neuronal wiring, learning, and behavior. Of the known epigenetic regulatory paradigms, functional state is coded in the form of covalent post-translational modifications of DNA, protein and/or RNA. Because the substrates of these reactions (e.g., acetylation and J. A. Pospisilik (*) Department of Epigenetics, Max-Panck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany e-mail: [email protected]
methylation) are metabolites of energy metabolism, epigenetic regulation has an intimate link with metabolic state. Indeed, some of the most well-characterized influences of epigenetics on complex mammalian physiology are found in research on the metabolic syndrome, a collection of related pathologies including cardiovascular disease, obesity and insulin resistance. In this review series, the latest concepts bridging metabolism, chromatin, and metabolic disease are reviewed. They highlight the current state-of-the-art as well as some key questions waiting to be answered. Our own contribution, Teperino et al., gives a simple introduction to the molecular concepts of epigenetics and describes how recent technological advances have opened the door for disease “Epigenomics”. This is followed by a trio of reviews focusing on the dynamics of primarily histone and DNA modification in metabolism, aging, and senescence. Cosentino et al. focus on acetylation dynamics in aging and cancer, and on one of the
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