HP1 drives de novo 3D genome reorganization in early Drosophila embryos (ChIP-seq)

The genome of the fertilized egg becomes structurally and functionally reorganized during early embryogenesis. This includes the segregation of active and inactive chromosome regions into A and B compartments, which are a fundamental feature of genome organization in both vertebrates and invertebrates. Mutually exclusive and attractive interactions within each compartment are thought to contribute to compartment formation1,2. However, the molecular nature of compartmental forces, and thus how compartments form, remain unknown. Here we show that HP1a is a major driver of compartmental segregation in Drosophila early development. Depletion of HP1a leads to an overall decrease of compartmentalization and increased intra-chromosomal interactions. Polymer modeling analysis of Hi-C data and ChIP-seq suggest that establishment of the B compartment is driven by HP1a-mediated attractive interactions. Thus, HP1 controls the establishment of higher order 3D structure during early embryogenesis.