Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY.
J Cell Biol. 2018 Jul 2;217(7):2247-2259. doi: 10.1083/jcb.201803061. Epub 2018 May 14.
Dynamic regulation of gene expression in response to changing local conditions is critical for the survival of all organisms. In metazoans, coherent regulation of gene expression programs underlies the development of functionally distinct cell lineages. The cooperation between transcription factors and the chromatin landscape enables precise control of gene expression in response to cell-intrinsic and cell-extrinsic signals. Many of the chemical modifications that decorate DNA and histones are adducts derived from intermediates of cellular metabolic pathways. In addition, several of the enzymes that can remove these marks use metabolites as part of their enzymatic reaction. These observations have led to the hypothesis that fluctuations in metabolite levels influence the deposition and removal of chromatin modifications. In this review, we consider the emerging evidence that cellular metabolic activity contributes to gene expression and cell fate decisions through metabolite-dependent effects on chromatin organization.
动态调节基因表达以响应不断变化的局部条件对于所有生物体的生存至关重要。在后生动物中，基因表达程序的协调调节是功能不同的细胞谱系发育的基础。转录因子与染色质景观之间的合作使基因表达能够在细胞内和细胞外信号的作用下进行精确调控。许多修饰 DNA 和组蛋白的化学修饰物是细胞代谢途径中间产物的加合物。此外，一些可以去除这些标记的酶将代谢物作为其酶反应的一部分。这些观察结果导致了这样一种假设，即代谢物水平的波动会影响染色质修饰的沉积和去除。在这篇综述中，我们考虑了新兴的证据，即细胞代谢活性通过代谢物对染色质组织的影响，有助于基因表达和细胞命运决定。
