Characterization of factors that underlie transcriptional silencing in C. elegans oocytes.
Characterization of factors that underlie transcriptional silencing in C. elegans oocytes.
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DOI：
10.1371/journal.pgen.1010831
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发表时间：
2023-07
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
虽然几十年来人们已经认识到，前驱阻滞的卵母细胞在全球水平上是转录沉默的，但促进沉默的分子途径仍然难以捉摸。先前对秀丽隐杆线虫的研究表明，拓扑异构酶II （TOP-2）和凝聚素II与H3K9me异染色质途径协同作用，在L1饥饿期间沉默种系基因的表达，而pie1蛋白沉默了早期胚胎p谱系的基因组。在这里，我们发现所有这三种沉默系统，TOP-2/凝缩素II， H3K9me和PIE-1，都是卵母细胞转录抑制所必需的。我们发现沉默期间染色质上的H3K9me3标记显著增加，并且沉默是受细胞周期控制的。我们还发现PIE-1在沉默之前定位于核仁，而沉默期间核仁的溶解依赖于TOP-2/冷凝蛋白II。我们的数据确定了卵母细胞中基因组沉默的分子成分和触发因素，并建立了PIE-1核仁驻留与其抑制转录能力之间的联系。在大多数动物中，当卵母细胞接近成熟和受精时，卵发生涉及全基因组的转录抑制。虽然在完全成熟的卵母细胞中转录抑制在20世纪60年代初首次被记录，但促进基因组沉默的分子参与者尚未被确定。在这里，我们研究了线虫，我们发现三个先前定义的基因组沉默系统都在成熟前的卵母细胞中工作，并且都是沉默所必需的。第一个系统，拓扑异构酶II与凝聚蛋白II复合物一起作用，促进卵母细胞染色质的超压实，这可能解释了它在基因组沉默中的作用。第二种是修饰染色质以产生异染色质的系统的组成部分，它也驱动卵母细胞染色质的压实。有趣的是，第三个系统——PIE-1蛋白——是沉默所必需的，而不是染色质压缩所必需的。我们的数据表明，虽然染色质压实是卵母细胞基因组沉默所必需的，但这还不够。我们的研究为这些途径如何在全球水平上沉默基因表达的机制分析打开了大门。
While it has been appreciated for decades that prophase-arrested oocytes are transcriptionally silenced on a global level, the molecular pathways that promote silencing have remained elusive. Previous work in C. elegans has shown that both topoisomerase II (TOP-2) and condensin II collaborate with the H3K9me heterochromatin pathway to silence gene expression in the germline during L1 starvation, and that the PIE-1 protein silences the genome in the P-lineage of early embryos. Here, we show that all three of these silencing systems, TOP-2/condensin II, H3K9me, and PIE-1, are required for transcriptional repression in oocytes. We find that H3K9me3 marks increase dramatically on chromatin during silencing, and that silencing is under cell cycle control. We also find that PIE-1 localizes to the nucleolus just prior to silencing, and that nucleolar dissolution during silencing is dependent on TOP-2/condensin II. Our data identify both the molecular components and the trigger for genome silencing in oocytes and establish a link between PIE-1 nucleolar residency and its ability to repress transcription. In most animals, oogenesis involves a genome-wide repression of transcription as oocytes approach maturation and fertilization. While transcriptional repression in fully grown oocytes was first documented in the early 1960s, the molecular players that promote genome silencing had yet to be identified. Here, we study the round worm C. elegans and we find that three previously defined genome silencing systems are all operational in pre-maturation oocytes and are all required for silencing. The first system, topoisomerase II acting together with the condensin II complex, promotes a hyper compaction of oocyte chromatin, which likely explains its role in genome silencing. The second, components of a system that modifies chromatin to produce heterochromatin, also drives compaction of the oocyte chromatin. Interestingly, the third system—the PIE-1 protein—is required for silencing but not for chromatin compaction. Our data show that while chromatin compaction is required for genome silencing in oocytes, it is not sufficient. Our studies open the door to more mechanistic analysis of how these pathways can silence gene expression on a global level.
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DOI：
10.1073/pnas.80.10.2926
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DAVIS, FM;TSAO, TY;RAO, PN
通讯作者：
RAO, PN
DOI：
10.1083/jcb.149.4.811
发表时间：
2000-05-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Freeman L;Aragon-Alcaide L;Strunnikov A
通讯作者：
Strunnikov A
通过有丝分裂维持转录特异性。
DOI：
10.1146/annurev-genom-121321-094603
发表时间：
2022-08-31
影响因子：
8.7
作者：
通讯作者：
--
影响因子：
4.6
作者：
Burrows, AE;Sceurman, BK;Golden, A
通讯作者：
Golden, A
影响因子：
4.5
作者：
Bessler JB;Andersen EC;Villeneuve AM
通讯作者：
Villeneuve AM