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器官发育过程中的可变启动子使用。

Alternative promoter usage during organ development.

作者信息

Tan Jiang, Sun Yidan

机构信息

Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America.

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America.

出版信息

PLoS Genet. 2025 Mar 28;21(3):e1011635. doi: 10.1371/journal.pgen.1011635. eCollection 2025 Mar.

Abstract

Dynamic gene expression is crucial for mammalian organ development, influencing organ-specific functions and responses. A significant number of mammalian protein-coding genes are regulated by multiple distinct promoters, suggesting that the choice of promoter is as critical as its transcriptional output. However, the role of alternative promoters in organ development remains largely unexplored. In this study, we utilized RNA-seq data from 313 mouse samples across various developmental stages in seven major organs to identify active promoters. Our analyses revealed between 967 and 3,237 developmentally dynamic promoters (DDPs) in each organ. These DDPs encompass not only major promoters with the highest activity within a gene but also alternative promoters with lower activity, which are often overlooked in traditional gene-level analyses. Notably, we found that alternative DDPs can be independently regulated compared to their major counterparts, suggesting the involvement of unique transcriptional regulatory mechanisms. Furthermore, we observed that increased alternative promoter usage plays a pivotal role in driving organ-specific functions and gene expression alterations. Our findings underscore the importance of alternative promoter usage in shaping organ identity and function, providing new insights into the regulatory complexity of organogenesis.

摘要

动态基因表达对于哺乳动物器官发育至关重要,影响着器官特异性功能和反应。大量哺乳动物蛋白质编码基因受多个不同启动子调控,这表明启动子的选择与其转录输出同样关键。然而,可变启动子在器官发育中的作用在很大程度上仍未得到探索。在本研究中,我们利用来自七个主要器官不同发育阶段的313个小鼠样本的RNA测序数据来鉴定活性启动子。我们的分析揭示了每个器官中有967至3237个发育动态启动子(DDP)。这些DDP不仅包括基因内活性最高的主要启动子,还包括活性较低的可变启动子,而这些可变启动子在传统基因水平分析中常常被忽视。值得注意的是,我们发现可变DDP与其主要对应物相比可以独立调控,这表明存在独特的转录调控机制。此外,我们观察到可变启动子使用增加在驱动器官特异性功能和基因表达改变中起关键作用。我们的研究结果强调了可变启动子使用在塑造器官特性和功能中的重要性,为器官发生的调控复杂性提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4931/11978060/15c904727d5d/pgen.1011635.g001.jpg

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