First Author | Chen Z | Year | 2024 |
Journal | Nat Genet | Volume | 56 |
Issue | 4 | Pages | 675-685 |
PubMed ID | 38509385 | Mgi Jnum | J:347410 |
Mgi Id | MGI:7622067 | Doi | 10.1038/s41588-024-01681-2 |
Citation | Chen Z, et al. (2024) Increased enhancer-promoter interactions during developmental enhancer activation in mammals. Nat Genet 56(4):675-685 |
abstractText | Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here we investigate the three-dimensional (3D) conformation of enhancers during mammalian development by generating high-resolution tissue-resolved contact maps for nearly a thousand enhancers with characterized in vivo activities in ten murine embryonic tissues. Sixty-one percent of developmental enhancers bypass their neighboring genes, which are often marked by promoter CpG methylation. The majority of enhancers display tissue-specific 3D conformations, and both enhancer-promoter and enhancer-enhancer interactions are moderately but consistently increased upon enhancer activation in vivo. Less than 14% of enhancer-promoter interactions form stably across tissues; however, these invariant interactions form in the absence of the enhancer and are likely mediated by adjacent CTCF binding. Our results highlight the general importance of enhancer-promoter physical proximity for developmental gene activation in mammals. |