Identification of TSIX, encoding an RNA antisense to human XIST, reveals differences from its murine counterpart: Implications for X inactivation

X inactivation is the mammalian method for X-chromosome dosage compensation , but some features of this developmental process vary among mammals. Such species variations provide insights into the essential components of the pa thway. Tsix encodes a transcript antisense to the murine Xist transcript an d is expressed in the mouse embryo only during the initial stages of X inac tivation; it has been shown to play a role in imprinted X inactivation in t he mouse placenta. We have identified its counterpart within the human X in activation center (XIC). Human TSIX produces a >30-kb transcript that is ex pressed only in cells of fetal origin; it is expressed from human XIC trans genes in mouse embryonic stem cells and from human embryoid-body-derived ce lls, but not from human adult somatic cells. Differences in the structure o f human and murine genes indicate that human TSIX was truncated during evol ution. These differences could explain the fact that X inactivation is not imprinted in human placenta, and they raise questions about the role of TSI X in random X inactivation.