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DOI 10.1007/s00018-013-1292-6 Cellular and Molecular Life SciencesCell. Mol. Life Sci. (2013) 70:1493–1494

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

methylation) are metabolites of energy metabolism, epige-netic 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 metabo-lism, 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 techno-logical advances have opened the door for disease “Epig-enomics”. This is followed by a trio of reviews focusing on the dynamics of primarily histone and DNA modifica-tion in metabolism, aging, and senescence. Cosentino et al. focus on acetylation dynamics in aging and cancer, and on one of the best-characterized groups of chromatin regula-tors studied in metabolic regulation, histone deacetylases. Encompassing the added dimension of DNA methylation, Ciacchiera et al. provide a parallel update on methylation–metabolism crosstalk, and, in a very timely review, Posavec and colleagues highlight the somewhat underappreciated class of Macro domain proteins, a direct energy sensory system located within the chromatin template itself.

Inevitably, medically driven epigenetic research will con-tinue to grow rapidly in the coming years. Three additional reviews in this series drive towards the epigenetic core of mammalian pathophysiology. What is clear is that there are still many more questions than answers. In a detailed view of developmental reprogramming and endocrine pancreas biology, Sandovici and colleagues highlight how perturba-tions during fetal developmental represent an ultra-sensitive window of plasticity and carry what are believed to be

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 iden-tification of multiple epigenetic regulatory niveaus, previ-ously 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 “chro-matin 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 capa-ble 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, func-tional state is coded in the form of covalent post-transla-tional 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, Germanye-mail: pospisilik@ie-freiburg.mpg.de

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decades-long consequences for metabolic fitness in humans. Huidobro et al. review the multiple faces of human genetic mutation directly impinging upon epigenetic control, a clear case for pivotal human disease relevance. And, finally, Mary-Elizabeth Patti focuses our current understanding of how metabolic disease etiology is subject to parental nutri-tional state control, raising what are surely some of the most pressing scientific questions in our attempt to understand modern-day metabolic disease.

This series brings together ideas from a field that is still in its infancy. They touch on the roots of the current epi-demic of metabolic disease, a trillion-dollar global socio-economic issue. Indeed, it will be interesting to see to what extent charting epigenetic cellular memory systems will open the door for novel, even preventative, options for com-batting metabolic disease.