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发育过程中嵌套基因对宿主基因的诱导作用。

Induction of host genes by nested genes during development.

作者信息

Soulavie Fabien, Couillault Carole, Melki Matéo, Buyannemekh Khulganaa, Barrière Antoine, Villoutreix Paul, Bertrand Vincent

机构信息

Aix Marseille University, CNRS, IBDM, Turing Center for Living Systems, Marseille, France.

Aix Marseille University, Université de Toulon, CNRS, LIS, Turing Centre for Living Systems, Marseille, France.

出版信息

iScience. 2025 Jun 27;28(8):113021. doi: 10.1016/j.isci.2025.113021. eCollection 2025 Aug 15.

Abstract

Embryonic development relies on tightly controlled gene expression. In this study, we analyzed the transcriptional effect during development of a striking genomic topology, the opposite nested configuration, where a gene is located in an intron of a host gene in the opposite direction. Using CRISPR genome engineering and single molecule FISH, we characterized the regulatory interactions between , a transcription factor involved in neuronal specification, and its host , a DNA repair enzyme, showing that the nested gene induces transcription of a short version of its host in neurons. Extending our analysis to the hundreds of protein coding genes in opposite nested configuration and using single-cell RNA-seq data covering embryogenesis, we observed that coexpression between nested and host genes is relatively common especially in cells positive for the nested gene. Our study illustrates how the presence of a nested gene can influence expression of its host.

摘要

胚胎发育依赖于严格控制的基因表达。在本研究中,我们分析了一种引人注目的基因组拓扑结构——反向嵌套构型(即一个基因以相反方向位于宿主基因的内含子中)在发育过程中的转录效应。利用CRISPR基因组工程和单分子荧光原位杂交技术,我们对参与神经元特化的转录因子及其宿主(一种DNA修复酶)之间的调控相互作用进行了表征,结果表明该嵌套基因可诱导其宿主的一个短版本在神经元中进行转录。将我们的分析扩展到数百个处于反向嵌套构型的蛋白质编码基因,并使用涵盖胚胎发生的单细胞RNA测序数据,我们观察到嵌套基因与其宿主基因之间的共表达相对常见,尤其是在对嵌套基因呈阳性的细胞中。我们的研究阐明了嵌套基因的存在如何影响其宿主基因的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/12274878/fb0c5824a05f/gr1.jpg

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