Eleftheria Parasyraki, Medhavi Mallick, Victoria Hatch, Viviana Vastolo, Michael U. Musheev, Emil Karaulanov, Alexandr Gopanenko, Simon Moxon, Maria Méndez-Lago, Dandan Han, Lars Schomacher, Debasish Mukherjee, Christof Niehrs
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引用次数: 0
Abstract
5-Methylcytosine (5mC) is an established epigenetic mark in vertebrate genomic DNA, but whether its oxidation intermediates formed during TET-mediated DNA demethylation possess an instructive role of their own that is also physiologically relevant remains unresolved. Here, we reveal a 5-formylcytosine (5fC) nuclear chromocenter, which transiently forms during zygotic genome activation (ZGA) in Xenopus and mouse embryos. We identify this chromocenter as the perinucleolar compartment, a structure associated with RNA Pol III transcription. In Xenopus embryos, 5fC is highly enriched on Pol III target genes activated at ZGA, notably at oocyte-type tandem arrayed tRNA genes. By manipulating Tet and Tdg enzymes, we show that 5fC is required as a regulatory mark to promote Pol III recruitment as well as tRNA expression. Concordantly, 5fC modification of a tRNA transgene enhances its expression in vivo. The results establish 5fC as an activating epigenetic mark during zygotic reprogramming of Pol III gene expression.
5-甲基胞嘧啶(5mC)是脊椎动物基因组 DNA 中一个公认的表观遗传标记,但其在 TET 介导的 DNA 去甲基化过程中形成的氧化中间产物是否具有与生理相关的指导作用仍未解决。在这里,我们发现了一个 5-甲酰基胞嘧啶(5fC)核染色中心,它在章鱼和小鼠胚胎的子代基因组激活(ZGA)过程中瞬时形成。我们确定该染色中心为核周区室,这是一种与 RNA Pol III 转录相关的结构。在章鱼胚胎中,5fC 在 ZGA 激活的 Pol III 目标基因上高度富集,尤其是在卵母细胞型串联排列 tRNA 基因上。通过操纵 Tet 和 Tdg 酶,我们发现 5fC 是促进 Pol III 招募和 tRNA 表达所必需的调控标记。同时,对 tRNA 转基因进行 5fC 修饰可增强其在体内的表达。这些结果确立了 5fC 在 Pol III 基因表达的合子重编程过程中是一个激活的表观遗传标记。
期刊介绍:
Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO).
The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries.
In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.