Human x inactivation center induces random X chromosome inactivation in male transgenic mice

X chromosome inactivation is the means to down-regulate the transcriptional output of X chromosomes in female mammals. Essential DNA from the murine X inactivation center (Xic) has been identified by introducing it into male embryonic stem (ES) cells. To identify the essential sequences on human X c hromosomes, we transfected male mouse ES cells with a YAC transgene contain ing 480 kb of the putative human X inactivation center (XIC). Despite littl e DNA sequence conservation, the human transgene is recognized as a second Xic in these XY mouse cells and induces random inactivation in chimeric mic e derived from these cells. Inactivation is extensive on the X chromosome, but more localized on chromosome 11 carrying the transgene, demonstrating t hat initial inactivation and spreading of inactivation signals along the ch romosome are independent events. Our results show for the first time that t he DNA included in the human XIC transgene is sufficient to initiate random X inactivation, even in cells of another species. Interspecies XIC trangen es should facilitate further investigation of this process in humans and ot her mammals. (C) 1999 Academic Press.