Mews P, Berger S L
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Methods Enzymol. 2016;574:311-329. doi: 10.1016/bs.mie.2016.04.002. Epub 2016 May 31.
Metabolic state and chromatin structure are tightly linked, enabling adaptation of gene expression to changing environment and metabolism. The bioenergetic pathways and enzymes that provide metabolic cofactors for histone modification have recently emerged as central regulators of chromatin. Current research therefore focuses on the dynamic interface of cellular metabolism and chromatin structure. Here, we provide an adaptable approach to examine broadly in changing physiological states, how chromatin structure is dynamically modulated by metabolic activity. We employ two complementary methods: high-throughput sequencing to establish the location of epigenetic changes, and stable isotope tracing using mass spectrometry to evaluate chromatin modification dynamics. Our two-pronged approach is of particular advantage when interrogating how metabolic and oncogenic mutations influence the dynamic relationship between metabolism, nutritional environment, and chromatin regulation.
代谢状态与染色质结构紧密相连，使得基因表达能够适应不断变化的环境和代谢。为组蛋白修饰提供代谢辅因子的生物能量途径和酶最近已成为染色质的核心调节因子。因此，当前的研究聚焦于细胞代谢与染色质结构的动态界面。在此，我们提供一种适应性方法，以广泛研究在不断变化的生理状态下，染色质结构如何被代谢活动动态调节。我们采用两种互补方法：高通量测序以确定表观遗传变化的位置，以及使用质谱的稳定同位素示踪来评估染色质修饰动态。当探究代谢和致癌突变如何影响代谢、营养环境与染色质调控之间的动态关系时，我们的双管齐下方法具有特别的优势。
