GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo.
GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo.
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DOI：
10.7554/elife.66668
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发表时间：
2021-03-15
期刊：
影响因子：
7.7
通讯作者：
Harrison MM
中科院分区：
文献类型：
--
作者：
Gaskill MM;Gibson TJ;Larson ED;Harrison MM
受精后，生殖细胞的基因组被重新编程以形成全能胚胎。先锋转录因子是重塑染色质和驱动合子基因表达的初始波所必需的。在黑腹果蝇中，先驱因子塞尔达对于经历这一戏剧性的重新编程时期的发育至关重要，这一时期被称为母体到合子过渡（MZT）。然而，尚不清楚这一过渡是否需要额外的先驱因素。我们通过MZT，GAGA因子（GAF）确定了发育所需的额外母系编码因子。GAF是激活广泛的合子转录和重塑染色质可及性景观所必需的。我们证明了塞尔达优先控制最早转录基因的表达，而广泛激活过程中表达的基因主要依赖于GAF。因此，通过MZT的进展需要协调多个先驱样的因素，我们建议，随着开发的进行，控制权逐渐从塞尔达转移到GAF。生物体中的大多数细胞共享完全相同的遗传信息，但它们仍然采用不同的身份。这种多样性的出现是因为在细胞中的任何给定时间只有一组基因被打开。锁定在DNA上的蛋白质通过在正确的时间激活某些基因来控制这种特异性。然而，要发挥这一作用，它们首先需要物理访问DNA：这可能很困难，因为遗传信息是紧密压缩的，因此它可以适合细胞。一组蛋白质可以帮助解开基因组，以发现随后可以访问和激活的基因。虽然这些“先驱因子”因此可以塑造细胞的身份，但关于它们如何共同努力做到这一点，还有很多未知之处。例如，先驱因子塞尔达在早期果蝇发育中至关重要，因为它使卵子和精子的遗传信息经历戏剧性的重新编程并产生新的生物体。然而，尚不清楚这一过渡是否需要额外的助手。利用这种动物系统，Gaskill、吉布森等人鉴定出GAGA因子是一种蛋白质，它与塞尔达一起打开并重新编程果蝇胚胎基因组中沿着的数百个不同部分。这个标签团队的努力始于塞尔达最初对激活基因的重要性;然后将调控交给GAGA因子继续这一过程。如果没有蛋白质，胚胎就会死亡。在苍蝇发育过程中瞥见早期遗传事件提供了通常适用于其他动物（如鱼类和哺乳动物）的见解。最终，这项研究可能有助于科学家了解人类胚胎中的问题。
Following fertilization, the genomes of the germ cells are reprogrammed to form the totipotent embryo. Pioneer transcription factors are essential for remodeling the chromatin and driving the initial wave of zygotic gene expression. In Drosophila melanogaster, the pioneer factor Zelda is essential for development through this dramatic period of reprogramming, known as the maternal-to-zygotic transition (MZT). However, it was unknown whether additional pioneer factors were required for this transition. We identified an additional maternally encoded factor required for development through the MZT, GAGA Factor (GAF). GAF is necessary to activate widespread zygotic transcription and to remodel the chromatin accessibility landscape. We demonstrated that Zelda preferentially controls expression of the earliest transcribed genes, while genes expressed during widespread activation are predominantly dependent on GAF. Thus, progression through the MZT requires coordination of multiple pioneer-like factors, and we propose that as development proceeds control is gradually transferred from Zelda to GAF. Most cells in an organism share the exact same genetic information, yet they still adopt distinct identities. This diversity emerges because only a selection of genes is switched on at any given time in a cell. Proteins that latch onto DNA control this specificity by activating certain genes at the right time. However, to perform this role they first need to physically access DNA: this can be difficult as the genetic information is tightly compacted so it can fit in a cell. A group of proteins can help to unpack the genome to uncover the genes that can then be accessed and activated. While these ‘pioneer factors’ can therefore shape the identity of a cell, much remains unknown about how they can work together to do so. For instance, the pioneer factor Zelda is essential in early fruit fly development, as it enables the genetic information of the egg and sperm to undergo dramatic reprogramming and generate a new organism. Yet, it was unclear whether additional helpers were required for this transition. Using this animal system, Gaskill, Gibson et al. identified GAGA Factor as a protein which works with Zelda to open up and reprogram hundreds of different sections along the genome of fruit fly embryos. This tag-team effort started with Zelda being important initially to activate genes; regulation was then handed over for GAGA Factor to continue the process. Without either protein, the embryo died. Getting a glimpse into early genetic events during fly development provides insights that are often applicable to other animals such as fish and mammals. Ultimately, this research may help scientists to understand how things can go wrong in human embryos.