Essential role of Cp190 in physical and regulatory boundary formation

Boundaries in animal genomes delimit contact domains with enhanced internal contact frequencies and have debated functions in limiting regulatory cross-talk between domains and guiding enhancers to target promoters. Most mammalian boundaries form by stalling of chromosomal loop-extruding cohesin by CTCF, but most Drosophila boundaries form CTCF independently. However, how CTCF-independent boundaries form and function remains largely unexplored. Here, we assess genome folding and developmental gene expression in fly embryos lacking the ubiquitous boundary-associated factor Cp190. We find that sequence-specific DNA binding proteins such as CTCF and Su(Hw) directly interact with and recruit Cp190 to form most promoter-distal boundaries. Cp190 is essential for early development and prevents regulatory cross-talk between specific gene loci that pattern the embryo. Cp190 was, in contrast, dispensable for long-range enhancer-promoter communication at tested loci. Cp190 is thus currently the major player in fly boundary formation and function, revealing that diverse mechanisms evolved to partition genomes into independent regulatory domains.

Automated summary

Boundaries in animal genomes play a crucial role in limiting regulatory cross-talk and guiding enhancers to target promoters. This study reveals that the formation and function of boundaries in flies are different from mammals. Unlike mammalian boundaries, most Drosophila boundaries form independently of CTCF and are recruited by Cp190. These boundaries are essential for early development and prevent regulatory cross-talk between specific gene loci, but are dispensable for long-range enhancer-promoter communication.