A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome.

X chromosome inactivation (XCI) is the random silencing of one X chromosome in females to achieve gene dosage balance between the sexes. As a result, all females are heterozygous for X-linked gene expression. One of the key regulators of XCI is Xist, which is essential for the initiation and maintenance of XCI.

Visualization of Xist Long Noncoding RNA with a Fluorescent CRISPR/Cas9 System.

X-inactive specific transcript (Xist) is a long noncoding RNA that is essential for initiating and maintaining epigenetic silencing of one copy of the X chromosome in mammalian females. But the mechanism by which Xist localizes and spreads on the X chromosome and facilitates transcriptional silencing remains largely unknown. This limited understanding, at least in part, is due to the technical difficulties in the visualization and functional characterization of Xist.

Pharmacological reactivation of inactive X-linked in cerebral cortical neurons of living mice.

Rett syndrome (RTT) is a genetic disorder resulting from a loss-of-function mutation in one copy of the X-linked gene methyl-CpG-binding protein 2 (). Typical RTT patients are females and, due to random X chromosome inactivation (XCI), ∼50% of cells express mutant MECP2 and the other ∼50% express wild-type MECP2. Cells expressing mutant MECP2 retain a wild-type copy of MECP2 on the inactive X chromosome (Xi), the reactivation of which represents a potential therapeutic approach for RTT.