Enhancer-promoter interactions become more instructive in the transition from cell-fate specification to tissue...

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Enhancer elements regulate gene expression by physically interacting with target gene promoters.
• The dynamic relationship between enhancer-promoter (E-P) proximity and gene activity is not fully understood, with varied observed correlations.
• Understanding this relationship is crucial for deciphering gene regulatory mechanisms during development.

Purpose of the Study:

• To investigate the temporal dynamics of enhancer-promoter (E-P) proximity and its correlation with gene activity during Drosophila embryogenesis.
• To differentiate between permissive and instructive roles of E-P interactions in cell-fate specification versus tissue differentiation.

Main Methods:

• Utilized Capture-C technology on FACS-purified myogenic and neurogenic cells from Drosophila embryos.
• Analyzed 600 characterized enhancers and promoters with known tissue-specific activity.
• Compared E-P proximity and activity states (OFF-to-ON and ON-to-OFF) during cell specification and differentiation.

Main Results:

• Observed conserved E-P topologies between specified muscle and neuronal cells, independent of gene activity.
• Identified the emergence of new distal interactions during tissue differentiation, correlating with changes in gene activity.
• Demonstrated a shift in E-P regulatory modes from permissive to instructive as development progresses.

Conclusions:

• E-P proximity plays a permissive role during early cell-fate specification, with topology uncoupled from activity.
• During terminal tissue differentiation, E-P proximity becomes instructive, directly coupled to gene activation.
• The mode of enhancer-promoter interaction dynamically changes throughout embryogenesis to regulate gene expression.