Institute for Predictive and Personalized Medicine of Cancer (IMPPC), Crta. Can Ruti, Cami de les Escoles, 08916 Badalona, Barcelona, Spain.
Cell Mol Life Sci. 2013 May;70(9):1509-24. doi: 10.1007/s00018-013-1294-4. Epub 2013 Mar 3.
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.
代谢和表观遗传学如何在分子水平上相互联系和调节尚不清楚。在这篇综述中，我们将讨论直接代谢物与染色质成分和修饰物结合作为一种可能的调节机制的作用。我们将重点讨论球形宏观结构域，这是一种进化上高度保守的蛋白质折叠，可以识别 NAD(+)衍生的代谢物。宏观结构域存在于组蛋白变体、组蛋白修饰物和染色质重塑因子等蛋白质中。在这里，我们总结了含有宏观结构域的染色质蛋白和生成相关代谢物的酶。我们将重点讨论组蛋白变体 macroH2A，进一步讨论代谢物结合对染色质功能的可能影响。
