Chromatin as a key consumer in the metabolite economy
Chromatin as a key consumer in the metabolite economy
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DOI：
10.1038/s41589-020-0517-x
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发表时间：
2020-06-01
影响因子：
14.8
通讯作者：
Muir, Tom W.
中科院分区：
文献类型：
--
作者：
Diehl, Katharine L.;Muir, Tom W.
这一视角强调了通过染色质对基因组和新陈代谢的相互调控中出现的新主题，包括非酶组蛋白修饰、辅因子混杂染色质修饰酶和亚核质代谢物池。在真核生物中，染色质重塑和翻译后修饰(PTM)塑造局部染色质景观，在基因组内建立允许和抑制区域，与其他表观遗传机制协调转录、复制和DNA修复。尽管细胞营养信号包含大量的途径，但最近的注意力转向了一种假设，即细胞的新陈代谢状态是通过核内代谢物的类型和浓度传递给基因组的，这些代谢物是染色质修饰酶的辅助因素。重要的是，表观遗传和代谢失调都是一系列疾病的特征，这种代谢-染色质轴可能会产生一系列新的治疗靶点。在这个视角下，我们重点介绍了通过染色质对基因组和代谢进行相互调控的新主题，包括化学反应代谢物引起的非酶性组蛋白修饰，辅因子混杂染色质修饰酶的PTM多样性的扩大，以及亚核质代谢物库的存在和重要性的证据。
This Perspective highlights emerging themes in the inter-regulation of the genome and metabolism via chromatin, including nonenzymatic histone modifications, cofactor-promiscuous chromatin-modifying enzymes, and subnucleocytoplasmic metabolite pools.In eukaryotes, chromatin remodeling and post-translational modifications (PTMs) shape the local chromatin landscape to establish permissive and repressive regions within the genome, orchestrating transcription, replication, and DNA repair in concert with other epigenetic mechanisms. Though cellular nutrient signaling encompasses a huge number of pathways, recent attention has turned to the hypothesis that the metabolic state of the cell is communicated to the genome through the type and concentration of metabolites in the nucleus that are cofactors for chromatin-modifying enzymes. Importantly, both epigenetic and metabolic dysregulation are hallmarks of a range of diseases, and this metabolism-chromatin axis may yield a well of new therapeutic targets. In this Perspective, we highlight emerging themes in the inter-regulation of the genome and metabolism via chromatin, including nonenzymatic histone modifications arising from chemically reactive metabolites, the expansion of PTM diversity from cofactor-promiscuous chromatin-modifying enzymes, and evidence for the existence and importance of subnucleocytoplasmic metabolite pools.