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

• 成果类型: Article
• 署名作者: Eder, Mathias; Moene, Christina J. I.; Dauban, Lise; Magnitov, Mikhail; Drayton, Jamie; de Haas, Marcel; Leemans, Christ; Verkuilen, Martijn; de Wit, Elzo; Hansen, Anders S.; van Steensel, Bas
• 署名单位: Netherlands Cancer Institute; Netherlands Cancer Institute; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9497
• DOI: 10.1126/science.ads6552
• 发表日期: 2025-09-18
• 关键词: domains

摘要

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 similar to 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.