Abstract
The tight correlation between topologically associating domains (TADs) and epigenetic domains in Drosophila suggests that the epigenome contributes to define TADs. However, it is still unknown whether histone modifications are essential for TAD formation and structure. By either deleting or shifting key regulatory elements needed to establish the epigenetic signature of Polycomb TADs, we show that the epigenome is not a major driving force for the establishment of TADs. On the other hand, physical domains have an important impact on the formation of epigenetic domains, as they can restrict the spreading of repressive histone marks and looping between cis-regulatory elements.