小柯机器人

日本庆应义塾大学医学院Haruhiko Siomi团队发现，MERVL（鼠内源性逆转录病毒-L）逆转录转座子的转录是着床前胚胎发育所必需的。2023年3月2日出版的《自然—遗传学》杂志发表了这一最新研究成果。

研究人员发现，全长而不是编码逆转录病毒蛋白的MERVL转录本对于胚胎着床前发育过程中准确调节宿主转录组和染色质状态至关重要。由于分化和基因组稳定性缺陷，敲低和基于CRISPRi的MERVL抑制都会导致胚胎致死。

此外，转录组和表观基因组分析表明，MERVL转录本缺失会导致二细胞特异性基因亚群保持染色质可及性状态和异常表达。综上所述，该研究结果提出了一个模型，其中内源性逆转录病毒在调节宿主细胞命运过程中起着关键作用。

据悉，合子基因组激活（ZGA）是受精后关键的一步，可促进细胞全能性并调节胚胎发育过程中不同的细胞命运。MERVL在ZGA二细胞时期短暂上调。尽管MERVL表达被认作是细胞全能性的标志，但这种逆转录转座子在小鼠胚胎发生中的功能仍然未知。

附：英文原文

Title: Transcription of MERVL retrotransposons is required for preimplantation embryo development

Author: Sakashita, Akihiko, Kitano, Tomohiro, Ishizu, Hirotsugu, Guo, Youjia, Masuda, Harumi, Ariura, Masaru, Murano, Kensaku, Siomi, Haruhiko

Issue&Volume: 2023-03-02

Abstract: Zygotic genome activation (ZGA) is a critical postfertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL (murine endogenous retrovirus-L) is transiently upregulated at the two-cell stage during ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remains elusive. Here, we show that full-length MERVL transcripts, but not encoded retroviral proteins, are essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development. Both knockdown and CRISPRi-based repression of MERVL result in embryonic lethality due to defects in differentiation and genomic stability. Furthermore, transcriptome and epigenome analysis revealed that loss of MERVL transcripts led to retention of an accessible chromatin state at, and aberrant expression of, a subset of two-cell-specific genes. Taken together, our results suggest a model in which an endogenous retrovirus plays a key role in regulating host cell fate potential.

DOI: 10.1038/s41588-023-01324-y

Source: https://www.nature.com/articles/s41588-023-01324-y

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex