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MERVL 逆转录转座子的转录对于胚胎植入前的发育是必需的。

Transcription of MERVL retrotransposons is required for preimplantation embryo development.

机构信息

Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan.

Human Biology Microbiome Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo, Japan.

出版信息

Nat Genet. 2023 Mar;55(3):484-495. doi: 10.1038/s41588-023-01324-y. Epub 2023 Mar 2.

DOI:10.1038/s41588-023-01324-y
PMID:36864102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10011141/
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.

摘要

合子基因组激活（ZGA）是一个关键的受精后步骤，它促进了全能性，并允许在发育中的胚胎中出现不同的细胞命运。在 ZGA 期间，MERVL（鼠内源性逆转录病毒-L）在两细胞期短暂上调。尽管 MERVL 表达被广泛用作全能性的标志物，但这种逆转录病毒在小鼠胚胎发生中的作用仍然难以捉摸。在这里，我们表明全长 MERVL 转录本，但不是编码的逆转录病毒蛋白，对于在植入前发育过程中宿主转录组和染色质状态的准确调节是必不可少的。MERVL 的敲低和基于 CRISPRi 的抑制都会导致胚胎致死，原因是分化和基因组稳定性缺陷。此外，转录组和表观基因组分析表明，MERVL 转录本的缺失导致在二细胞特异性基因的一部分上保持可及染色质状态和异常表达。总之，我们的结果表明，内源性逆转录病毒在调节宿主细胞命运潜能方面起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/9959f2dffbe1/41588_2023_1324_Fig13_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/9959f2dffbe1/41588_2023_1324_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/0cc6d6b58b60/41588_2023_1324_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/858e7473cd56/41588_2023_1324_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/e2117a064778/41588_2023_1324_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/02a9d4e9ad21/41588_2023_1324_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/f7352ca176ba/41588_2023_1324_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/67828cb07a1f/41588_2023_1324_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/b7ea7e4dc92e/41588_2023_1324_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/8f395998261f/41588_2023_1324_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/bc3d92f9d3b7/41588_2023_1324_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/be0553fd8c85/41588_2023_1324_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/68dd2b91cfc7/41588_2023_1324_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/29e8cceecf92/41588_2023_1324_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d609/10011141/9959f2dffbe1/41588_2023_1324_Fig13_ESM.jpg

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