Functional maps of a genomic locus reveal confinement of an enhancer by its target gene.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40966339.
- Also identified by DOI 10.1126/science.ads6552 and PMC identifier 7618358.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Sox2</i> gene and its distal enhancer. This revealed an intricate, sharply confined activation landscape in which the native <i>Sox2</i> 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 <i>Sox2</i> 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.
Medical subject headings
- Enhancer Elements, Genetic
- SOXB1 Transcription Factors
- Genetic Loci