The Drosophila embryo as a tabula rasa for the epigenome.
The Drosophila embryo as a tabula rasa for the epigenome.
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DOI：
10.12703/r/11-40
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发表时间：
2022
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真核生物中基因表达的控制依赖于转录因子和RNA聚合酶如何操纵染色质的结构。随着基因表达程序的改变，这些相互作用在发育中特别重要。染色质通常限制DNA的可及性，因此暴露调控元件处的序列对于基因表达至关重要。然而，理解转录因子如何操纵染色质结构和调控事件的序列是具有挑战性的。果蝇胚胎提供了一个强大的设置，直接观察染色质特征的建立和阐述，并通过实验测试许多后生动物之间共享的转录事件的因果关系。大胚胎通过活体成像是易于处理的，并且各种发达的工具允许在早期发育期间操纵因素。早期胚胎发育为合胞体，具有快速的核分裂，没有合子转录，染色质基本上没有特征。因此，该系统中的研究揭示了由先驱因子触发的基因组激活的进展，所述先驱因子启动DNA在调控元件处的暴露以及染色质结构域（包括异染色质、核仁和核体）的建立。在早期胚胎中从头出现的核结构揭示了染色质动力学的特征，这些特征可能是所有细胞中转录调控的核心。
The control of gene expression in eukaryotes relies on how transcription factors and RNA polymerases manipulate the structure of chromatin. These interactions are especially important in development as gene expression programs change. Chromatin generally limits the accessibility of DNA, and thus exposing sequences at regulatory elements is critical for gene expression. However, it is challenging to understand how transcription factors manipulate chromatin structure and the sequence of regulatory events. The Drosophila embryo has provided a powerful setting to directly observe the establishment and elaboration of chromatin features and experimentally test the causality of transcriptional events that are shared among many metazoans. The large embryo is tractable by live imaging, and a variety of well-developed tools allow the manipulation of factors during early development. The early embryo develops as a syncytium with rapid nuclear divisions and no zygotic transcription, with largely featureless chromatin. Thus, studies in this system have revealed the progression of genome activation triggered by pioneer factors that initiate DNA exposure at regulatory elements and the establishment of chromatin domains, including heterochromatin, the nucleolus, and nuclear bodies. The de novo emergence of nuclear structures in the early embryo reveals features of chromatin dynamics that are likely to be central to transcriptional regulation in all cells.