The Drosophila embryo as a tabula rasa for the epigenome.

Faculty reviews Pub Date : 2022-12-23 eCollection Date: 2022-01-01 DOI:10.12703/r/11-40
Kami Ahmad, Steven Henikoff
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引用次数: 5

Abstract

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.

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果蝇胚胎是表观基因组的原型。
真核生物的基因表达控制依赖于转录因子和 RNA 聚合酶如何操纵染色质结构。随着基因表达程序的变化,这些相互作用在发育过程中尤为重要。染色质通常会限制 DNA 的可及性,因此暴露调控元件上的序列对基因表达至关重要。然而,要了解转录因子如何操纵染色质结构和调控事件的顺序却很有挑战性。果蝇胚胎提供了一个强大的环境,可以直接观察染色质特征的建立和细化,并通过实验检验许多后生动物共有的转录事件的因果关系。大型胚胎可通过活体成像进行操作,而各种完善的工具可在早期发育过程中对各种因素进行操作。早期胚胎发育为一个合胞体,核分裂迅速,没有合子转录,染色质基本上没有特征。因此,在该系统中进行的研究揭示了基因组激活的进展过程,这种进展是由先驱因子触发的,先驱因子启动 DNA 暴露于调控元件,并建立染色质域,包括异染色质、核仁和核体。早期胚胎核结构的新生揭示了染色质动力学的特征,这些特征可能是所有细胞转录调控的核心。
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