Gene Arrangement Shapes Transcriptional Responses to DNA Supercoiling in a Multicellular Organism [RNA-seq]

In contrast to transcription initiation, transcription elongation defects are not driven by neighboring transcription but by local supercoiling generated by the gene’s own transcription. These elongation effects are not accompanied by global changes in elongation-associated histone modifications but coincide with modest reductions in promoter and enhancer marks. We find that negative supercoiling promotes coordinated expression of divergent gene pairs, while positive supercoiling uncouples expression of convergent genes.

Our results indicate that the relative orientation and spacing between genes modulate how DNA supercoiling propagates through chromatin, revealing a directional mechanism by which genome architecture contributes to coordinated expression of genes in a multicellular eukaryotic genome.