Enhancer-promoter proximity predicts transcriptional competence but not transcriptional output in the Drosophila brain
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.
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BibTeX
@misc{messina2026enhancerpromoter,
title = {{Enhancer-promoter proximity predicts transcriptional competence but not transcriptional output in the Drosophila brain}},
author = {Olivier Messina and Loucif Remini and Christopher H. Bohrer and Jean-Bernard Fiche and Jean-Charles Walter and Andrea Parmeggiani and Marcelo Nollmann},
howpublished = {arXiv},
year = {2026},
month = sep,
doi = {10.48550/arxiv.2609.03058},
eprint = {2609.03058},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2609.03058},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - UNPB
TI - Enhancer-promoter proximity predicts transcriptional competence but not transcriptional output in the Drosophila brain
AU - Olivier Messina
AU - Loucif Remini
AU - Christopher H. Bohrer
AU - Jean-Bernard Fiche
AU - Jean-Charles Walter
AU - Andrea Parmeggiani
AU - Marcelo Nollmann
PY - 2026
DA - 2026/09/02
PB - arXiv
DO - 10.48550/arxiv.2609.03058
UR - https://arxiv.org/abs/2609.03058
AB - 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.
ER -