| Authors |
Chen, Zhuoxin , Snetkova, Valentina , Bower, Grace , Jacinto, Sandra , Clock, Benjamin , Dizehchi, Atrin , Barozzi, Iros , Mannion, Brandon J. , Alcaina-Caro, Ana , LÓPEZ-RÍOS MORENO, JAVIER, Dickel, Diane E. , Visel, Axel , Pennacchio, Len A. , Kvon, Evgeny Z. |
| Abstract |
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.\n A catalog of enhancer-promoter (E-P) interactions across ten mouse embryonic tissues, supported by in vivo functional experiments, shows that E-P proximity increases upon enhancer activation during development. |
