Convergent pairs of highly transcribed genes restrict chromatin looping in Dictyostelium discoideum.

Abstract

Dictyostelium discoideum is a unicellular slime mold, developing into a multicellular fruiting body upon starvation. Development is accompanied by large-scale shifts in gene expression program, but underlying features of chromatin spatial organization remain unknown. Here, we report that the Dictyostelium 3D genome is organized into positionally conserved, largely consecutive, non-hierarchical and weakly insulated loops at the onset of multicellular development. The transcription level within the loop interior tends to be higher than in adjacent regions. Loop interiors frequently contain functionally linked genes and genes which coherently change expression level during development. Loop anchors are predominantly positioned by the genes in convergent orientation. Results of polymer simulations and Hi-C-based observations suggest that the loop profile may arise from the interplay between transcription and extrusion-driven chromatin folding. In this scenario, a convergent gene pair serves as a bidirectional extrusion barrier or a 'diode' that controls passage of the cohesin extruder by relative transcription level of paired genes.