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Transcription bodies regulate gene expression by sequestering CDK9
Nature Cell Biology ( IF 21.3 ) Pub Date : 2024-04-08 , DOI: 10.1038/s41556-024-01389-9
Martino Ugolini , Maciej A. Kerlin , Ksenia Kuznetsova , Haruka Oda , Hiroshi Kimura , Nadine L. Vastenhouw

The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells. It remains unclear, however, if and how transcription bodies affect gene expression. Here we disrupted the formation of two prominent endogenous transcription bodies that mark the onset of zygotic transcription in zebrafish embryos and analysed the effect on gene expression using enriched SLAM-seq and live-cell imaging. We find that the disruption of transcription bodies results in the misregulation of hundreds of genes. Here we focus on genes that are upregulated. These genes have accessible chromatin and are poised to be transcribed in the presence of the two transcription bodies, but they do not go into elongation. Live-cell imaging shows that disruption of the two large transcription bodies enables these poised genes to be transcribed in ectopic transcription bodies, suggesting that the large transcription bodies sequester a pause release factor. Supporting this hypothesis, we find that CDK9—the kinase that releases paused polymerase II—is highly enriched in the two large transcription bodies. Overexpression of CDK9 in wild-type embryos results in the formation of ectopic transcription bodies and thus phenocopies the removal of the two large transcription bodies. Taken together, our results show that transcription bodies regulate transcription by sequestering machinery, thereby preventing genes elsewhere in the nucleus from being transcribed.



中文翻译:

转录体通过隔离 CDK9 调节基因表达

转录活性在特化转录体中的定位是真核细胞中基因表达的标志。然而,目前尚不清楚转录体是否以及如何影响基因表达。在这里,我们破坏了斑马鱼胚胎中两个标志合子转录开始的显着内源转录体的形成,并使用富集 SLAM-seq 和活细胞成像分析了对基因表达的影响。我们发现转录体的破坏导致数百个基因的失调。在这里,我们关注上调的基因。这些基因具有可接近的染色质,并准备在两个转录体存在的情况下进行转录,但它们不会延伸。活细胞成像显示,两个大转录体的破坏使得这些平衡基因能够在异位转录体中转录,这表明大转录体隔离了暂停释放因子。支持这一假设的是,我们发现 CDK9(释放暂停聚合酶 II 的激酶)在两个大转录体中高度富集。 CDK9在野生型胚胎中的过度表达导致异位转录体的形成,从而表现出两个大转录体的去除。总而言之,我们的结果表明转录体通过隔离机制调节转录,从而阻止细胞核其他地方的基因被转录。

更新日期:2024-04-08
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