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Comprehensive spatiotemporal DNA methylation analysis of mouse tissue and organ progression through fetal development to adulthood†.
Biology of Reproduction ( IF 3.1 ) Pub Date : 2020-09-09 , DOI: 10.1093/biolre/ioaa163
Elizabeth Elder 1, 2 , Serge McGraw 1, 2, 3
Affiliation  

The precise and timely expression of genes, starting as soon as initial fertilization and continuously throughout fetal tissue progression, is crucial to ensure the proper development of mammalian embryos [1]. The synergy between epigenetic modifications and the binding of specific transcription factors (TFs) to gene regulatory elements is primarily responsible for coordinating this dynamic spatiotemporal regulation of genes in the developing embryo [2]. DNA methylation, an epigenetic modification essential for mammalian development, is the biochemical process by which a methyl chemical group is added to cytosines that are typically immediately followed by a guanine (mCG), which will generally negatively influence gene expression [3]. It can also occur in an mCH context (i.e., CpA, CpT, and CpC), although this role remains obscure thus far. To thoroughly comprehend the impact of DNA methylation on gene regulation in the embryo, it is imperative to integrate other epigenetic marks (histone modifications, chromatin accessibility) as they form an interconnected network, as well as consider their location within the genome (e.g., promoter, enhancer, and gene body) and their timing during developmental stages. As part of the mouse Encyclopedia of DNA Elements (ENCODE) project, a group led by Joseph R. Ecker of the Salk Institute has addressed an important gap in knowledge in postimplantation developmental epigenomics in a recent paper published in Nature [4]. They characterized 168 methylomes to which they integrated histone modification and chromatin accessibility data from published companion papers [5, 6] to generate a comprehensive spatiotemporal epigenomic map of 12 mouse tissues and organs at 9 developmental stages from embryogenesis (E10.5-P0) to adulthood (Figure 1A). This work is the first of its kind in providing an important multiomic resource for studying the gene regulation of fetal tissues and organs through time.

中文翻译:

从胎儿发育到成年的小鼠组织和器官进展的综合时空 DNA 甲基化分析†。

从初始受精开始并在整个胎儿组织进展过程中持续准确、及时地表达基因,对于确保哺乳动物胚胎的正常发育至关重要 [1]。表观遗传修饰与特定转录因子 (TF) 与基因调控元件的结合之间的协同作用主要负责协调发育中胚胎中基因的这种动态时空调控 [2]。DNA 甲基化是哺乳动物发育必不可少的表观遗传修饰,是将甲基化学基团添加到胞嘧啶的生化过程,通常紧随其后的是鸟嘌呤 (mCG),这通常会对基因表达产生负面影响 [3]。它也可以出现在 mCH 上下文中(即 CpA、CpT 和 CpC),尽管到目前为止这个角色仍然模糊不清。为了彻底理解 DNA 甲基化对胚胎基因调控的影响,必须整合其他表观遗传标记(组蛋白修饰、染色质可及性),因为它们形成一个相互关联的网络,并考虑它们在基因组中的位置(例如,启动子) 、增强子和基因体)及其在发育阶段的时间。作为小鼠 DNA 元素百科全书 (ENCODE) 项目的一部分,由索尔克研究所的 Joseph R. Ecker 领导的一个小组在最近发表于 以及考虑它们在基因组中的位置(例如,启动子、增强子和基因体)以及它们在发育阶段的时间。作为小鼠 DNA 元素百科全书 (ENCODE) 项目的一部分,由索尔克研究所的 Joseph R. Ecker 领导的一个小组在最近发表于 以及考虑它们在基因组中的位置(例如,启动子、增强子和基因体)以及它们在发育阶段的时间。作为小鼠 DNA 元素百科全书 (ENCODE) 项目的一部分,由索尔克研究所的 Joseph R. Ecker 领导的一个小组在最近发表于自然[4]。他们对 168 个甲基化组进行了表征,他们将已发表的配套论文 [5, 6] 中的组蛋白修饰和染色质可及性数据整合到其中,以生成从胚胎发生 (E10.5-P0) 到 9 个发育阶段的 12 个小鼠组织和器官的综合时空表观基因组图谱。成年(图 1A)。这项工作首次为研究胎儿组织和器官的基因调控提供了重要的多组学资源。
更新日期:2020-11-04
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