Xist, the X inactive-specific transcript, is a long noncoding (lnc)RNA gene. It is the master regulator of X chromosome inactivation (XCI) in mammals, a crucial dosage-compensation mechanism between the sex chromosomes of males and females. Xist RNA accumulates along the chromosome from which it is transcribed, recruiting factors to modify chromatin and silence X-linked genes in cis. This process involves associated RNA-binding proteins (RBPs) and downstream pathways for chromatin modification and gene silencing [1].

In adult human B cells, XIST is continuously required to silence a subset of X-linked immune genes like TLR7, and XIST-dependent genes lack promoter DNA methylation and rely on continuous XIST-dependent histone deacetylation [2]. In naive human pluripotent stem cells (hPSCs), XIST spreads across the X chromosome, dampening X-linked gene expression, and also targets specific autosomal regions, inducing repressive chromatin changes and gene expression dampening [3]. XIST has also been implicated in the development and prognosis of brain tumors, such as gliomas, playing pathophysiological roles in processes like migration, proliferation, angiogenesis, chemoresistance, and evasion of apoptosis [4].

In conclusion, Xist is essential for X chromosome inactivation, equalizing X-linked gene dosage between male and female cells. Its dysregulation is associated with various diseases, including those in the immune system, pluripotent cell-related conditions, and brain cancers. The study of Xist in models helps in understanding its complex functions in normal development and disease-associated processes.