A paper recently published in Nature reports silencing of one chromosome 21 in Down syndrome cells. Using genome editing with zinc finger nucleases, the authors inserted an inducible XIST (the X-inactivation gene) on chromosome 21 in Down syndrome pluripotent stem cells. The XIST non-coding RNA coated chromosome 21 and triggered stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a ‘chromosome 21 Barr body’. Notably, deficits in proliferation and neural rosette formation were rapidly reversed upon silencing one chromosome 21. This study provides a model to study human chromosome inactivation and creates a system to investigate genomic expression changes and cellular pathologies of trisomy 21, free from genetic and epigenetic noise. Successful trisomy silencing in vitro may also be the first step towards potential development of ‘chromosome therapy’.
Posted by Nicola Brunetti-Pierri, MD