Mapping promoter-enhancer interactions at the Drosophila shavenbaby locus

Cis-regulatory elements encoded in the genome play a central role in the spatio-temporal regulation of gene expression. A prominent example of a cis-regulatory element are enhancers which activate transcription in a cell-specific context and independent of their genomic location and orientation. Enhancers modulate transcription by mediating the binding of sequence-specific transcription factors and by communicating their state of occupancy to their target gene promoters. Enhancers can be located at great genomic distances from their cognate promoter. One of the longstanding questions in enhancer biology relates to how the physical interactions between enhancers and promoters are established to regulate gene expression assisted by transcription factors and how these interactions are regulated at different developmental contexts.

In this study, we have used the shavenbaby/ovo (svb) gene as a model system to elucidate the mechanisms of enhancer-promoter interactions during Drosophila embryogenesis. The svb gene encodes a transcription factor that controls the expression of multiple downstream effectors that collectively modulate actin dynamics, epidermal cell differentiation, and trichome formation. Systematic genetic dissection has identified seven enhancers, scattered in a gene desert of ⁓90 kb upstream of the svb promoter, that regulate its embryonic expression. Here we use cell-type specific chromosome conformation capture sequencing (4C-seq) strategy to identify the genomic interactions of the svb promoter and enhancers, and to determine how they interact in different cellular contexts within the developing embryo. This study will provide a pavement to deeper insights into the genomic architecture requirements for shavenbaby enhancer function across space and time.