Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B.
Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B.
复制标题
DOI：
10.7554/elife.30201
复制
发表时间：
2017-11-07
期刊：
影响因子：
7.7
通讯作者：
Seydoux G
中科院分区：
文献类型：
--
作者：
Lee CS;Lu T;Seydoux G
Nanos RNA 结合蛋白是后生动物种系发育所必需的，但其潜在机制仍知之甚少。我们分析了秀丽隐杆线虫中缺乏纳米同源物 nos-1 和 nos-2 的原始生殖细胞 (PGC) 的转录组。 nos-1nos-2 PGC 无法沉默卵母细胞中正常表达的数百个转录本。我们发现这种失调是由于母体转录本的更新延迟和不适当的转录激活造成的。后者似乎是母系遗传的转录因子 LIN-15B 周转延迟的间接结果，LIN-15B 是一种已知能拮抗 PRC2 活性的 synMuvB 类转录因子。 PRC2 是种系染色质重编程所必需的，缺乏 PRC2 的 PGC 的转录组与 nos-1nos-2 PGC 的转录组相似。母体 LIN-15B 的缺失可恢复 nos-1nos-2 突变体的生育能力。这些发现表明 Nanos 通过下调母体 RNA 和蛋白质来促进生殖细胞的命运，否则母体 RNA 和蛋白质会干扰 PRC2 依赖性 PGC 染色质重编程。每个新胚胎都会从其母亲那里继承一套起始指令。这些说明被称为“母体嫁妆”，帮助受精卵度过最初的几个发育阶段。后来，母亲的嫁妆被移除，以便胚胎的遗传指令可以接管。在动物中，早期胚胎中的一些细胞变得专门产生卵子（技术上称为卵母细胞）或精子。这些细胞称为生殖细胞，它们是繁殖所必需的。一种名为 Nanos 的蛋白质可以帮助生殖细胞变得与其他细胞不同，但目前尚不清楚 Nanos 如何发挥这种作用。李等人。研究了秀丽隐杆线虫胚胎中的纳米粒子。在许多方面，线虫的早期发育与许多其他动物相同。通过检查没有 Nanos 的蠕虫，Lee 等人。结果表明，没有 Nanos 的生殖细胞不会失去母体嫁妆。因此，这些细胞仍然含有一种名为 LIN-15B 的分子，该分子可以在线虫体内产生其他类型的细胞。最终，如果没有 Nanos，生殖细胞就不会发育并死亡，从而使蠕虫不育。生殖细胞对于生物的繁殖和生育至关重要。了解它们是如何产生的可以让科学家们了解很多关于胚胎在出生前如何发育的知识。这最终可能有助于提高濒危物种的生育能力或治疗人类不育症。
Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin. Every new embryo inherits a set of starting instructions from its mother. These instructions are called a ‘maternal dowry’ and help a fertilized egg through the first few stages of development. Later, the maternal dowry is removed so that the embryo’s genetic instructions can take over. In animals, some of the cells in this early embryo become specialized to produce eggs (technically called oocytes) or sperm. These cells are called germ cells, and they are needed for reproduction. A protein called Nanos helps germ cells become different to other cells, but it is not clear how Nanos has this effect. Lee et al. studied Nanos in the embryos of the worm Caenorhabditis elegans. In many ways, early development is the same in the worm as in many other animals. By examining worms that did not have Nanos, Lee et al. showed that germ cells without Nanos do not lose their maternal dowry. As a result, the cells still contain a molecule called LIN-15B, which makes other types of cells in the worm. Ultimately, without Nanos, the germ cells do not develop and die leaving the worm sterile. Germ cells are essential for living things to reproduce and have children. Understanding how they are created can teach scientists a lot about how embryos develop before birth. This could eventually help to boost fertility in endangered species or to treat human sterility.