Transcription and Cohesin Direct Domain Boundary Spatial Positioning and are Linked to Friedreich's Ataxia

Ashley Karnay, Ricardo Linares-Saldana, Qiaohong Wang, Zachary Gardner, Jialiu A. Liang, Garrett T. Santini, Krishna Kumar Haridhasapavalan, Son C. Nguyen, Siewert Hugelier, Bhavana Shewale, Masato T. Kanemaki, Jill S. Napierala, Marek Napierala, Robert B. Wilson, Nicole Dubois, Andrey Poleshko, Wonho Kim, Parisha P. Shah, Melike Lakadamyali, Eric F. Joyce, Rajan Jain, Transcription and cohesin direct domain boundary spatial positioning and are linked to Friedreich’s ataxia, Molecular Cell, 2026, DOI: 10.1016/j.molcel.2026.04.019. 

These results suggest that gene silencing in Friedreich's ataxia is reinforced by where the gene sits in the nucleus," said Ashley Karnay, Ph.D., a postdoctoral fellow in Cardiovascular Medicine and Cell & Developmental Biology and the study's lead author. "By changing that positioning, we can partially restore FXN gene activity in diseased cells." 

 While the findings are early and not a treatment, they point to genome organization itself as a contributor to disease and raise the exciting possibility that future therapies could work by changing how the DNA is organized inside the nucleus.

Transcription and Cohesin Direct Domain Boundary Spatial Positioning and are Linked to Friedreich's Ataxia