This project builds on our previous work exploring Polycomb-dependent epigenetic chromatin signatures in mouse cranial neural crest cells (Minoux et al., Science 2017). During cell migration, key transcription factor genes remain transcriptionally repressed but poised for activation. Specific cues trigger a switch from a poised to an active chromatin state in postmigratory cells, enabling position-specific transcriptional programs that drive facial structure development.
We recently mapped promoter-promoter and enhancer-promoter contacts by promoter capture HiC in premigratory and postmigratory cranial neural crest cells (Kessler et al., Nature Comm 2023. I will present unpublished findings showing that in premigratory progenitor cells a network of Polycomb 3D interactions is established between poised promoters and distal accessible tethering elements, maintaining genes repressed though ready for activation. Interestingly, this pre-formed 3D chromatin topology facilitates the subsequent de novo recruitment of active long-range enhancers in migrating cranial neural crest cells, in turn enabling promoters to switch to an active state and drive craniofacial morphogenesis.
This topological mechanism reveals that Polycomb repressive interactions establish a 3D chromatin framework to guide future gene activation in vivo during facial development. This mechanism may also provide a rationale to understand how multipotent early-stage neural crest cells become committed to specific morphogenetic programs in vivo that shape facial features.
