PRBB-CRG Sessions Guillaume Andrey

26/06/202612:00MARIE CURIEPRBB-CRG SessionsGuillaume AndreyUniversité de Genève"Temporal coordination of enhancers drives developmental gene regulatory trajectories"Host: Renée BeekmanAbstract:Enhancers are central to shaping gene expression during embryonic development, yet how their activities are coordinated over time to drive dynamic developmental programs remains poorly understood. Using cell type- and stage-resolved enhancer atlases together with single-locus genetic dissection in the mouse limb, we identify temporally restricted enhancer repertoires that act sequentially during development. We propose a regulatory trajectory framework in which early-acting enhancers initiate gene expression and establish permissive chromatin domains in progenitor cells, late-acting enhancers maintain transcription in differentiated descendants, and regulatory silencing terminates gene expression programs. At the Shox2 locus, a transgenic recorder reveals this temporal division of labor, with early enhancers initiating transcription and late enhancers sustaining it. We further show that enhancer activity is accompanied by dynamic changes in 3D chromatin topology, whereas silencing involves the loss of enhancer–promoter contacts and can be driven by HOXD13, a known antagonist of Shox2. Together, our findings demonstrate how temporally coordinated enhancer repertoires generate complex developmental expression patterns and establish a mechanistic framework for enhancer-mediated cellular memory across developmental time.