Thrilled to share our latest work, now in @ScienceMagazine! Exploring how #3DGenome organization controls #transcription dynamics during #development. A few highlights below! #InHoxWeTrust
@XinyangBing
Zachary Sisco
@J_Raimundo_
@Michal_Levo
Mike Levine
science.org/doi/10.1126/sc…
@XinyangBing
Zachary Sisco
@J_Raimundo_
@Michal_Levo
Mike Levine
science.org/doi/10.1126/sc…
The Drosophila genome is organized by 2 types of elements: tethers mediate focal contacts, while insulators establish #TAD boundaries. We used genome editing and live transcription imaging to explore their roles in the temporal regulation of #Hox gene expression in the embryo. 
Transcription of the endogenous Scr gene, live! Active transcription foci (white spots) appear in a narrow stripe of nuclei (blue) just prior to the onset of gastrulation. (Scr-MS2, MCP-GFP, His2A-RFP)
Dedicated tethering elements foster long-range #enhancer-promoter interactions, and are key to fast transcriptional activation kinetics. Deleting the distal tethering element (DTE) disrupts enhancer-promoter interactions, and delays Scr activation.
By contrast, insulators prevent regulatory interference by precluding inappropriate interactions with enhancers and silencers located in neighboring TADs. Removing insulators causes TAD fusions, and disrupts temporal expression patterns. But the loops are fine...
It even seems to actually do something! Genetic disruptions of genome organization lead to quantitative defects in the development of adult sex comb structures.
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