Chromatin architecture transitions from zebrafish sperm through early embryogenesis.

Chromatin architecture transitions from zebrafish sperm through early embryogenesis.
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DOI:
10.1101/gr.269860.120
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发表时间:
2021-06
期刊:
影响因子:
7
通讯作者:
Cairns BR
Cairns BR
中科院分区:
生物学1区
文献类型:
--
作者:
Wike CL;Guo Y;Tan M;Nakamura R;Shaw DK;Díaz N;Whittaker-Tademy AF;Durand NC;Aiden EL;Vaquerizas JM;Grunwald D;Takeda H;Cairns BR

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3D格式的染色质结构映射增加了我们对调控序列和基因表达如何在基因组中连接和调控的理解。3D染色质基因组在胚胎发育过程中表现出广泛的重塑,尽管大多数物种的卵裂期胚胎在合子基因组激活(前ZGA)之前缺乏结构,但据报道斑马鱼具有结构。在这里,我们的目的是确定染色体结构在父系/精子斑马鱼配子细胞,以辨别它是否类似或通知早期前ZGA斑马鱼胚胎染色质结构。首先,我们通过先进的低单元原位Hi-C评估了高阶架构。由组蛋白包装的斑马鱼精子的结构缺乏拓扑相关结构域,而是显示每1-2 Mbs重复的约150 kb的“铰链样”结构域,表明类似有丝分裂染色体的浓缩重复结构。前ZGA胚胎缺乏染色体结构,与先前的工作相反,并且仅在ZGA后发育结构。在后ZGA,我们发现染色质结构开始形成在一个小的接触域的中位数长度为1.90 kb。这些小的接触结构域在增强子(包括超级增强子)处建立,并且Ep 300 a(p300)和Crebbpa(CBP)活性的化学抑制降低组蛋白H3 K27 ac,但不抑制转录,减少这些接触。总之,这项研究揭示了组蛋白包装的斑马鱼精子染色质中的铰链样结构域,并确定了斑马鱼胚胎中高阶染色质结构的初始形成发生在ZGA之后,主要是在具有高H3 K27 ac的增强子处。
Chromatin architecture mapping in 3D formats has increased our understanding of how regulatory sequences and gene expression are connected and regulated in a genome. The 3D chromatin genome shows extensive remodeling during embryonic development, and although the cleavage-stage embryos of most species lack structure before zygotic genome activation (pre-ZGA), zebrafish has been reported to have structure. Here, we aimed to determine the chromosomal architecture in paternal/sperm zebrafish gamete cells to discern whether it either resembles or informs early pre-ZGA zebrafish embryo chromatin architecture. First, we assessed the higher-order architecture through advanced low-cell in situ Hi-C. The structure of zebrafish sperm, packaged by histones, lacks topological associated domains and instead displays “hinge-like” domains of ∼150 kb that repeat every 1–2 Mbs, suggesting a condensed repeating structure resembling mitotic chromosomes. The pre-ZGA embryos lacked chromosomal structure, in contrast to prior work, and only developed structure post-ZGA. During post-ZGA, we find chromatin architecture beginning to form at small contact domains of a median length of ∼90 kb. These small contact domains are established at enhancers, including super-enhancers, and chemical inhibition of Ep300a (p300) and Crebbpa (CBP) activity, lowering histone H3K27ac, but not transcription inhibition, diminishes these contacts. Together, this study reveals hinge-like domains in histone-packaged zebrafish sperm chromatin and determines that the initial formation of high-order chromatin architecture in zebrafish embryos occurs after ZGA primarily at enhancers bearing high H3K27ac.
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