Background: X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in
XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The
mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence
indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X
chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1) repeats are relatively enriched
on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for
efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of
silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes.
Results: Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key
determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are
relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are
silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that
chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X
chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could
confer the capacity for relatively efficient chromosome-wide silencing.
Conclusions: This study provides insight into the requirements for efficient Xist mediated silencing and specifically
identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major
influence on the ability of Xist-mediated silencing to be propagated in a continuous manner in cis.