Nucleolar-based Dux repression is essential for embryonic two-cell stage exit.
Nucleolar-based Dux repression is essential for embryonic two-cell stage exit.
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DOI：
10.1101/gad.349172.121
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发表时间：
2022-03-01
影响因子：
10.5
通讯作者：
Percharde M
中科院分区：
文献类型：
--
作者：
Xie SQ;Leeke BJ;Whilding C;Wagner RT;Garcia-Llagostera F;Low Y;Chammas P;Cheung NT;Dormann D;McManus MT;Percharde M
在这项研究中，Xie等人研究了哺乳动物胚胎中MERVL和两细胞（2C）基因上调的机制和要求，并报告了稳健的核糖体RNA（rRNA）合成和核仁成熟对于退出2C状态至关重要。他们的发现揭示了rRNA合成，核仁成熟和早期发育过程中基因抑制之间的有趣联系。受精后，哺乳动物胚胎必须从依赖母体转录物转变为转录自身基因组，在小鼠中，这涉及MERVL转座子和MERVL驱动基因在两细胞阶段的瞬时上调。MERVL和两细胞（2C）基因上调的机制和要求知之甚少。此外，这种MERVL驱动的转录程序必须迅速关闭，以允许两个细胞退出和发育进程。在这里，我们报告说，强大的核糖体RNA（rRNA）的合成和核仁成熟是必不可少的退出2C状态。2C样细胞和两细胞胚胎显示出相似的未成熟核仁，结构改变，rRNA产量减少。我们发现，核仁破坏通过阻断RNA聚合酶I活性或防止核仁相分离增强转换为2C样状态的胚胎干细胞（ESC）的MERVL激活剂Dux从核仁表面脱离。在胚胎中，核仁破坏会阻止适当的核仁成熟和Dux沉默，并导致2 - 4个细胞停滞。我们的研究结果揭示了一个有趣的rRNA合成之间的联系，核仁成熟，在早期发育过程中的基因抑制。
In this study, Xie et al. investigated the mechanisms and requirement for MERVL and two-cell (2C) gene up-regulation in mammalian embryos, and report that robust ribosomal RNA (rRNA) synthesis and nucleolar maturation are essential for exit from the 2C state. Their findings reveal an intriguing link between rRNA synthesis, nucleolar maturation, and gene repression during early development. Upon fertilization, the mammalian embryo must switch from dependence on maternal transcripts to transcribing its own genome, and in mice this involves the transient up-regulation of MERVL transposons and MERVL-driven genes at the two-cell stage. The mechanisms and requirement for MERVL and two-cell (2C) gene up-regulation are poorly understood. Moreover, this MERVL-driven transcriptional program must be rapidly shut off to allow two-cell exit and developmental progression. Here, we report that robust ribosomal RNA (rRNA) synthesis and nucleolar maturation are essential for exit from the 2C state. 2C-like cells and two-cell embryos show similar immature nucleoli with altered structure and reduced rRNA output. We reveal that nucleolar disruption via blocking RNA polymerase I activity or preventing nucleolar phase separation enhances conversion to a 2C-like state in embryonic stem cells (ESCs) by detachment of the MERVL activator Dux from the nucleolar surface. In embryos, nucleolar disruption prevents proper nucleolar maturation and Dux silencing and leads to two- to four-cell arrest. Our findings reveal an intriguing link between rRNA synthesis, nucleolar maturation, and gene repression during early development.
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DOI：
10.1126/science.aag1927
发表时间：
2017-02-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choi YJ;Lin CP;Risso D;Chen S;Kim TA;Tan MH;Li JB;Wu Y;Chen C;Xuan Z;Macfarlan T;Peng W;Lloyd KC;Kim SY;Speed TP;He L
通讯作者：
He L
影响因子：
64.5
作者：
Feric M;Vaidya N;Harmon TS;Mitrea DM;Zhu L;Richardson TM;Kriwacki RW;Pappu RV;Brangwynne CP
通讯作者：
Brangwynne CP
抑制RNA聚合酶I作为促进p53癌症特异性激活的治疗策略。
影响因子：
50.3
作者：
Bywater MJ;Poortinga G;Sanij E;Hein N;Peck A;Cullinane C;Wall M;Cluse L;Drygin D;Anderes K;Huser N;Proffitt C;Bliesath J;Haddach M;Schwaebe MK;Ryckman DM;Rice WG;Schmitt C;Lowe SW;Johnstone RW;Pearson RB;McArthur GA;Hannan RD
通讯作者：
Hannan RD
影响因子：
64.8
作者：
Beagrie RA;Scialdone A;Schueler M;Kraemer DC;Chotalia M;Xie SQ;Barbieri M;de Santiago I;Lavitas LM;Branco MR;Fraser J;Dostie J;Game L;Dillon N;Edwards PA;Nicodemi M;Pombo A
通讯作者：
Pombo A
影响因子：
30.8
作者：
Chuong, Edward B.;Rumi, M. A. Karim;Soares, Michael J.;Baker, Julie C.
通讯作者：
Baker, Julie C.