2024/11/20 by Mariam Museridze, Stefano Ceolin, Bettina Mühling +4 · 1 voice
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · #Developmental Biology and Gene Regulation #Genomics and Chromatin Dynamics #Plant Molecular Biology Research
paper · doi:10.1126/sciadv.adr9856
openalex publication_date 2024/11/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/24
The modularity of transcriptional enhancers is central to our understanding of morphological evolution, allowing specific changes to a gene expression pattern component, without affecting others. Enhancer modularity refers to physically separated stretches of regulatory sequence producing discrete spatiotemporal transcriptional activity. This concept stems from assays that test the sufficiency of a DNA segment to drive spatial reporter expression resembling that of the corresponding gene. Focusing on spatial patterns, it overlooks quantitative aspects of gene expression, underestimating the regulatory sequence actually required to reach full endogenous expression levels. Here, we show that five regulatory activities of the gene yellow in Drosophila , classically described as modular, result from extensively overlapping sequences, with broadly distributed regulatory information. Nevertheless, the independent regulatory activities of these entangled enhancers appear to be nucleated by specific segments that we called enhancer cores. Our work calls for a reappraisal of enhancer definition and properties, as well as of the consequences on regulatory evolution.