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

Science (New York, N.Y.)
Authors
Abstract

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 gene and its distal enhancer. This revealed an intricate, sharply confined activation landscape in which the native 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 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.

Year of Publication
2025
Journal
Science (New York, N.Y.)
Volume
389
Issue
6766
Pages
eads6552
Date Published
09/2025
ISSN
1095-9203
DOI
10.1126/science.ads6552
PubMed ID
40966339
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