XIST RNA and Architecture of the Inactive X Chromosome Implications for the Repeat Genome

XIST RNA paints and induces silencing of one X chromosome in mammalian female cells, providing a powerful model to investigate long-range chromosomal regulation. This chapter focuses on events downstream from the spread of XIST RNA across the interphase chromosome, to consider how this large noncoding RNA interacts with and silences a whole chromosome. Several lines of evidence are summarized that point to the involvement of repeat sequences in different aspects of the X-inactivation process. Although the "repeat genome" comprises close to half of the human genome, the potential for abundant repeats to contribute to genome regulation has been largely overlooked and may be underestimated. X inactivation has the potential to reveal roles of interspersed and other repeats in the genome. For example, evidence indicates that XIST RNA acts at the architectural level of the whole chromosome to induce formation of a silent core enriched for nongenic and repetitive (Cot-1) DNA, which corresponds to the DAPI-dense Barr body. Expression of repeat RNAs may contribute to chromosome remodeling, and evidence suggests that other types of repeat elements may be involved in escape from X inactivation. Despite great progress in decoding the rest of the genome, we suggest that the repeat genome may contain meaningful but complex language that remains to be better studied and understood.