近日，瑞士洛桑大学教授Nadine L. Vastenhouw小组的研究显示，转录体通过隔离CDK9调控基因表达。该项研究成果发表在2024年4月8日出版的《自然—细胞生物学》杂志上。

研究团队破坏了斑马鱼胚胎中两个突出的，标志着合子转录开始的内源性转录体的形成，通过富集的SLAM-测序和活细胞成像分析了对基因表达的影响。研究小组发现转录体的破坏导致数百个基因的错误调节。

课题组将重点放在上调的基因上。这些基因具有可接近的染色质，并且在两个转录体存在的情况下准备转录，但它们不进入延伸。活细胞成像显示，两个大的转录体的破坏使这些平衡的基因能够在异位转录体中转录，这表明大的转录体隔离了一种暂停释放因子。

为了支持这一假设，该课题组人员发现CDK9一种释放聚合酶II的激酶在两个大的转录体中高度富集。CDK9在野生型胚胎中的过度表达导致异位转录体的形成，其表型是两个大转录体的移除。综上所述，他们的研究结果表明，转录体通过隔离机制来调节转录，从而阻止细胞核中其他地方的基因被转录。

研究人员表示，转录活性在特化转录体中的定位是真核细胞基因表达的一个标志。然而，转录体是否以及如何影响基因表达仍不清楚。

附：英文原文

Title: Transcription bodies regulate gene expression by sequestering CDK9

Author: Ugolini, Martino, Kerlin, Maciej A., Kuznetsova, Ksenia, Oda, Haruka, Kimura, Hiroshi, Vastenhouw, Nadine L.

Issue&Volume: 2024-04-08

Abstract: 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 polymeraseII—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.

DOI: 10.1038/s41556-024-01389-9

Source: https://www.nature.com/articles/s41556-024-01389-9