The three-dimensional conformation of DNA in a cell has broad impacts on human health and disease — including in neurodevelopmental disorders caused by chromosomal abnormalities. Down syndrome caused by trisomy 21 is known to induce genome-wide transcriptional disruption. However, the consequences on the nuclear architecture and its interplay with the transcriptome have only recently been elucidated.
- Alterations to 3D genome conformation can affect transcriptional regulation in a wide range of disease states
- Trisomy 21 disrupts nuclear architecture and transcriptome of neural progenitors which display signatures of cellular senescence
- Senolytic therapeutics can ameliorate trisomy-21-associated molecular and cellular dysfunctions