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In a mini-review, Sundeep Kalantry describes new findings and outstanding questions in the field of X-chromosome inactivation -a paradigm of epigenetic inheritance. X-inactivation results in the mitotically-stable transcriptional silencing of genes along one of the two X-chromosomes in female mammals. How the cell distinguishes two identical chromosomal sequences to trigger inactivation of one X-chromosome while sparing the other and what the mechanisms are that propagate epigenetic inactivation as well as its prevention are among the major questions about X-inactivation that have long fascinated biologists. X-linked non-coding RNAs such as Xist and Tsix along with proteins of the Polycomb group play an essential role during X-inactivation. However, the precise contribution of these factors to the execution of the epigenetic states of the inactive-and the active-X remains unclear. Recent work indicates a finely-tuned requirement of these factors during X-inactivation, and posits that there likely are other factors that work in concert with these during X-inactivation. That X-inactivation only occurs in XX female cells and not in XY male cells is another challenging quest that has vexed X-inactivation enthusiasts. Quite intriguingly, recent developments suggest a role for the X-linked Rnf12 gene in the counting of the number of X-chromosomes -only when a certain threshold of RNF12 protein is reached, will X-inactivation be triggered. X-inactivation promises to continue to yield insights into fundamental epigenetic processes.
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