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Macro domains as metabolite sensors on chromatin

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Abstract

How metabolism and epigenetics are molecularly linked and regulate each other is poorly understood. In this review, we will discuss the role of direct metabolite-binding to chromatin components and modifiers as a possible regulatory mechanism. We will focus on globular macro domains, which are evolutionarily highly conserved protein folds that can recognize NAD+-derived metabolites. Macro domains are found in histone variants, histone modifiers, and a chromatin remodeler among other proteins. Here we summarize the macro domain-containing chromatin proteins and the enzymes that generate relevant metabolites. Focusing on the histone variant macroH2A, we further discuss possible implications of metabolite binding for chromatin function.

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Acknowledgments

We apologize to colleagues whose work could not be cited due to space limitations. The authors would like to thank Markus Hassler for his help in preparing the figures and Vincent Pasque, Harvey Evans, and members of the Buschbeck and Timinszky labs for their comments on the manuscript. Research in the Buschbeck lab is supported by Spanish MINECO grants (SAF2009-08496, SAF2012-39749 and RYC2010-07337). MP holds a predoctoral FI fellowship (AGAUR) and MB is a Ramón Y Cajal fellow (MINECO).

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  1. Institute for Predictive and Personalized Medicine of Cancer (IMPPC), Crta. Can Ruti, Cami de les Escoles, 08916, Badalona, Barcelona, Spain

    Melanija Posavec & Marcus Buschbeck

  2. Butenandt Institute of Physiological Chemistry, Ludwig Maximilian University of Munich, Butenandtstrasse 5, 81377, Munich, Germany

    Gyula Timinszky

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  1. Melanija Posavec
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Correspondence to Gyula Timinszky or Marcus Buschbeck.

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Posavec, M., Timinszky, G. & Buschbeck, M. Macro domains as metabolite sensors on chromatin. Cell. Mol. Life Sci. 70, 1509–1524 (2013). https://doi.org/10.1007/s00018-013-1294-4

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  • DOI: https://doi.org/10.1007/s00018-013-1294-4

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