Quantitative predictive value of enhancer–promoter proximity

Determine whether enrichment of enhancer–promoter proximal states at the Drosophila rutabaga locus quantitatively predicts transcriptional output among active neuronal subtypes, rather than merely distinguishing transcriptionally active from inactive cells.

Background

The study uses single-cell Hi-M imaging to analyze the rutabaga locus in adult Drosophila brain cells. It finds that transcriptionally active Kenyon cells are enriched for promoter-proximal enhancer configurations relative to non-Kenyon cells, supporting a role for enhancer–promoter proximity in establishing transcriptional competence.

The unresolved issue is whether this structural enrichment also specifies quantitative expression differences among active Kenyon-cell subtypes. The authors subsequently report that enhancer–promoter distance and the fraction of proximal states are poor predictors of rut transcriptional output across these active subtypes, but the passage explicitly identifies the broader predictive relationship as unclear.

References

Yet, whether this enrichment merely distinguishes active from inactive cells, or also quantitatively predicts transcriptional output among active neuronal subtypes, remains unclear.

— Enhancer-promoter proximity predicts transcriptional competence but not transcriptional output in the Drosophila brain  (2609.03058 - Messina et al., 2 Sep 2026) in Results, Section “A two-state model reveals transcription-dependent enrichment of E–P proximal states”