A stain upon the silence: Genes escaping X inactivation

X-chromosome inactivation is a remarkable epigenetic event in mammalian females that results in the transcriptional silencing of one of the pair of X chromosomes. However, not all X-linked genes are subject to inactivation, and in humans, the proportion of genes on the X chromosome that escapes inactivation is more than 15%. Here we examine the causes and consequences of failure to silence the entire X chromosome. We discuss the impact of the evolutionary history of the X (and Y) chromosome, and the bioinformatic approaches that promise to provide new insights into the genomic architecture of genes or regions that escape X-chromosome inactivation.