Transcription and Cohesin Direct Genome Positioning and Domain Boundary Plasticity

Consequently, our understanding of how compromised genome positioning leads to disease are limited. Here, we demonstrate that a cooperative relationship between gene transcription and cohesin activity directs lamina-associated domain (LAD) boundary plasticity and boundary-proximal gene spatial positioning.

Transcription mediates LAD boundary fidelity and loss of transcription repositions LAD-boundary genes to the nuclear lamina. The transcriptional repression-mediated repositioning is dependent on cohesin’s loop extrusion activity and cannot be linked to heterochromatin modifiers or compaction status. Further, pathogenic transcriptional silencing of the LAD-boundary gene FXN in Friedrich’s Ataxia is associated with improper peripheral positioning of FXN.