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The nexus of chromatin regulation and intermediary metabolism

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Abstract

Living organisms and individual cells continuously adapt to changes in their environment. Those changes are particularly sensitive to fluctuations in the availability of energy substrates. The cellular transcriptional machinery and its chromatin-associated proteins integrate environmental inputs to mediate homeostatic responses through gene regulation. Numerous connections between products of intermediary metabolism and chromatin proteins have recently been identified. Chromatin modifications that occur in response to metabolic signals are dynamic or stable and might even be inherited transgenerationally. These emerging concepts have biological relevance to tissue homeostasis, disease and ageing.

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Figure 1: DNA methylation and post-translational modifications of histones link metabolites and transcription.
Figure 2: Metabolic pathways of intermediary metabolism signal to chromatin.
Figure 3: Distinct modes of chromatin-mediated transcriptional control by intermediary metabolism products.
Figure 4: Metabolite influencers of complex biological systems.
Figure 5: Epigenetic drift and transgenerational inheritance of disease risks.

Change history

  • 10 December 2013

    The TCA cycle in Figure 2 has been corrected in the online version of this Review.

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Acknowledgements

We thank J. Carroll for graphics, G. Howard and A.-L. Lucido for editorial assistance, V. Fonseca and P. Cruz for administrative assistance. The authors are supported by funds from the Gladstone Institutes.

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E.V. is a member of the scientific advisory board of SIRTRIS/GSK

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Gut, P., Verdin, E. The nexus of chromatin regulation and intermediary metabolism. Nature 502, 489–498 (2013). https://doi.org/10.1038/nature12752

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