Enhancer-promoter proximity predicts transcriptional competence but not transcriptional output in the Drosophila brain
Year: 2026
Type: preprint
Abstract: How 3D genome architecture contributes to transcriptional specificity across neuronal cell types remains unclear. Here, we used multiplexed chromatin tracing to map chromatin architecture and cell identity at single-cell resolution in the adult Drosophila brain. We found that enhancer-promoter (E-P) proximity was increased in transcriptionally active compared with inactive neurons. Analysis of single traces revealed the existence of distinct proximal and distal E-P states, with active neurons enriched in the proximal state. However, this relationship broke down across active neuronal subtypes, where neither E-P proximity nor chromatin accessibility predicted transcriptional output. Thus, 3D genome organization distinguishes transcriptionally competent from inactive neuronal states without quantitatively specifying transcriptional output. Our findings support a model in which E-P proximity establishes a permissive structural state, while additional cell-type-specific regulatory mechanisms tune transcriptional output.
Source: arXiv (Cornell University)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: MUSE, G1185957321, G2441619162, G2450198060, G262592543, Deciphering how local mRNA translation impacts neurodegenerative diseases, G381665449, G5296751580, G5420063140, G6888366887, High-resolution mapping of cell type-specific 3D chromatin organization in a complex tissue, G703701052, G7080048889, G7240651115, G8082782559, G8087388668
OpenAlex ID: W7208783064