Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2019-10-30 , DOI: 10.1016/j.bbagen.2019.129454 Diletta Durano 1 , Francesca Di Felice 1 , Federica Caldarelli 1 , Andrea Lukacs 1 , Anna D'Alfonso 1 , Michele Saliola 1 , Fabio Sciubba 2 , Alfredo Miccheli 2 , Federico Zambelli 3 , Giulio Pavesi 3 , Marco E Bianchi 4 , Giorgio Camilloni 5
|
Background
The execution of many genetic programs, influenced by environmental conditions, is epigenetically controlled. Thus, small molecules of the intermediate metabolism being precursors of most of nutrition-deriving epigenetic modifications, sense the cell surrounding environment.
Methods
Here we describe histone H4K16 acetylation distribution in S. cerevisiae nhp6ab mutant, using ChIP-seq analysis; its transcription profile by RNA-seq and its metabolic features by studying the metabolome. We then intersected these three -omic approaches to unveil common crosspoints (if any).
Results
In the nhp6ab mutant, the glucose metabolism is switched to pathways leading to Acetyl-CoA synthesis. These enhanced pathways could lead to histone hyperacetylation altering RNA transcription, particularly of those metabolic genes that maintain high Acetyl-CoA availability.
Conclusions
Thus, the absence of chromatin regulators like Nhp6 A and B, interferes with a regulative circular mechanism where histone modification, transcription and metabolism influence each other and contribute to clarify the more general phenomenon in which gene regulation feeds metabolic alterations on epigenetic basis.
General significance
This study allowed us to identify, in these two factors, a common element of regulation in metabolism and chromatin acetylation state that could represent a powerful tool to find out relationships existing between metabolism and gene expression in more complex systems.
中文翻译：
酿酒酵母nhp6ab突变体中的组蛋白乙酰化景观反映了葡萄糖代谢的改变。
背景
受环境条件影响的许多遗传程序的执行在表观遗传上受到控制。因此，中间代谢的小分子是大多数营养衍生表观遗传修饰的前体，它们可感知细胞周围的环境。
方法
在这里，我们使用ChIP-seq分析描述酿酒酵母nhp6ab突变体中的组蛋白H4K16乙酰化分布；通过RNA seq分析其转录谱，并通过研究代谢组来了解其代谢特征。然后，我们将这三种组学方法相交，以揭示常见的交叉点（如果有）。
结果
在nhp6ab突变体中，葡萄糖代谢转换为导致乙酰辅酶A合成的途径。这些增强的途径可能导致组蛋白超乙酰化，从而改变RNA转录，特别是那些维持高乙酰辅酶A利用率的代谢基因。
结论
因此，缺乏染色质调节剂（如Nhp6 A和B）会干扰调节性循环机制，其中组蛋白修饰，转录和代谢相互影响，并有助于阐明更为普遍的现象，其中基因调节以表观遗传为基础来促进代谢改变。
一般意义
这项研究使我们能够从这两个因素中识别出代谢和染色质乙酰化状态的共同调控元素，这可能是一种功能强大的工具，可用来发现更复杂系统中代谢与基因表达之间的关系。
京公网安备 11010802027423号