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在 缺失时，促进合子基因组激活。

promotes zygotic genome activation upon loss of .

机构信息

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

Bioresource Engineering Division, Bioresource Center, RIKEN, Tsukuba, Japan.

出版信息

Elife. 2024 Jun 24;13:e95856. doi: 10.7554/eLife.95856.

DOI:10.7554/eLife.95856
PMID:38856708
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11196112/
Abstract

Once fertilized, mouse zygotes rapidly proceed to zygotic genome activation (ZGA), during which long terminal repeats (LTRs) of murine endogenous retroviruses with leucine tRNA primer (MERVL) are activated by a conserved homeodomain-containing transcription factor, DUX. However, -knockout embryos produce fertile mice, suggesting that ZGA is redundantly driven by an unknown factor(s). Here, we present multiple lines of evidence that the multicopy homeobox gene, , encodes a transcription factor that is highly expressed in mouse two-cell embryos and redundantly drives ZGA. Genome-wide profiling revealed that OBOX4 specifically binds and activates MERVL LTRs as well as a subset of murine endogenous retroviruses with lysine tRNA primer (MERVK) LTRs. Depletion of is tolerated by embryogenesis, whereas concomitant / depletion markedly compromises embryonic development. Our study identified OBOX4 as a transcription factor that provides genetic redundancy to preimplantation development.

摘要

一旦受精，小鼠受精卵迅速进入合子基因组激活（ZGA）阶段，在此期间，具有亮氨酸 tRNA 引物的小鼠内源性逆转录病毒的长末端重复序列（MERVL）被一个保守的含同源结构域的转录因子 DUX 激活。然而，-/- 胚胎产生可育的小鼠，这表明 ZGA 是由未知的因素（多个）冗余驱动的。在这里，我们提出了多条证据表明，多拷贝同源盒基因 OBOX4 编码一个转录因子，该转录因子在小鼠 2 细胞胚胎中高度表达，并冗余驱动 ZGA。全基因组分析显示，OBOX4 特异性结合并激活 MERVL LTR 以及一组具有赖氨酸 tRNA 引物（MERVK）LTR 的小鼠内源性逆转录病毒。/ 缺失胚胎发生是可以耐受的，而同时 / 缺失则显著损害胚胎发育。我们的研究确定了 OBOX4 作为一个转录因子，为植入前发育提供遗传冗余。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/3112f2920881/elife-95856-sa2-fig2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/b9ecd8570dff/elife-95856-sa2-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/3112f2920881/elife-95856-sa2-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/9a00dbbb9040/elife-95856-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/36bdfb34cda0/elife-95856-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/cd9220061767/elife-95856-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/714591b8be15/elife-95856-fig2-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/d081aca9cd44/elife-95856-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/2eeebb1d2bb5/elife-95856-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/ba17d92bed5f/elife-95856-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/cda9d46d2dc2/elife-95856-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/e8cd5b2e3fde/elife-95856-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/86a16b23bf16/elife-95856-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/420411c95b35/elife-95856-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/cb89d8138af7/elife-95856-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/08d2d91d7713/elife-95856-fig4-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/3d0c129da964/elife-95856-fig4-figsupp5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/299c7139ef45/elife-95856-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/76ab4e098240/elife-95856-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/b9ecd8570dff/elife-95856-sa2-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9886/11196112/3112f2920881/elife-95856-sa2-fig2.jpg

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