一个基因组位点的功能图谱揭示了增强子受其靶基因的限制

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-09-18 DOI:10.1126/science.ads6552

Mathias Eder, Christina J. I. Moene, Lise Dauban, Mikhail Magnitov, Jamie Drayton, Marcel de Haas, Christ Leemans, Martijn Verkuilen, Elzo de Wit, Anders S. Hansen, Bas van Steensel

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引用次数: 0

摘要

基因通常被位于较大基因组距离上的增强子激活，人们对这种定位的重要性知之甚少。通过将启动子-报告子结构重新定位到单个位点内的数千个替代位置，我们剖析了小鼠Sox2基因与其远端增强子之间的位置关系。这揭示了一个复杂的、严格限制的激活景观，在这个景观中，原生Sox2基因占据了其激活的最佳位置。基因的缺失放松了这种限制，并广泛地增加了报告基因的活性。Sox2基因的限制作用部分是由其约1千碱基编码区赋予的。我们的局部重新定位方法提供了基因组位点的高分辨率功能图谱，并揭示了基因可以强烈地限制其增强子的影响范围。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Functional maps of a genomic locus reveal confinement of an enhancer by its target gene

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Functional maps of a genomic locus reveal confinement of an enhancer by its target gene

Genes are often activated by enhancers located at large genomic distances, and the importance of this positioning is poorly understood. By relocating promoter-reporter constructs into thousands of alternative positions within a single locus, we dissected the positional relationship between the mouse Sox2 gene and its distal enhancer. This revealed an intricate, sharply confined activation landscape in which the native Sox2 gene occupies an optimal position for its activation. Deletion of the gene relaxes this confinement and broadly increases reporter activity. The confining effect of the Sox2 gene is partially conferred by its ~1-kilobase coding region. Our local relocation approach provides high-resolution functional maps of a genomic locus and reveals that a gene can strongly constrain the realm of influence of its enhancer.

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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