%0 Journal Article
%T Escape from X inactivation in mice and humans
%A Joel B Berletch
%A Fan Yang
%A Christine M Disteche
%J Genome Biology
%D 2010
%I BioMed Central
%R 10.1186/gb-2010-11-6-213
%X The difference in sex-chromosome make-up between mammalian males (XY) and females (XX) has led to the evolution of two main dosage-compensation mechanisms: upregulation of the active X chromosome (Xa) in both sexes to balance X expression with the autosomes; and inactivation of one X chromosome in females to avoid X hyperexpression and correct for the difference in gene dosage between the sexes [1-3] (see Table 1). These mechanisms evolved to compensate for the presence of only one copy (haploinsufficiency) of X-linked genes in males due to degeneration of the Y chromosome from its origin as an X homolog [4]. Suppression of recombination between the sex chromosomes was apparently mediated by large Y inversions, as deduced by remnant X/Y homology. This led to Y degeneration due to accumulation of mutations and inability to restore the correct DNA sequence [5,6]. Only small regions of homology and pairing between the sex chromosomes remain, called pseudoautosomal regions (PARs) because genes within these regions behave like autosomal genes.Initiation of X inactivation in female embryos depends on the transcription of the long noncoding RNA XIST/Xist (X-inactive specific transcript) from one chromosome (which will become the inactive X (Xi)) and recruitment of a protein complex important for X-chromosome silencing and heterochromatin formation [7,8]. In humans, XIST (17 kb in size) is located in the long arm of the X chromosome, whereas in mice where there is only one arm, Xist (15 kb in size) is in the middle of the chromosome. Xist RNA spreads along the X chromosome in cis and recruits a protein complex responsible for deposition of repressive histone modifications onto the Xi [9-11]. As a result the Xi becomes heterochromatic, silent and condensed. Before implantation, X inactivation is imprinted, with the paternal X chromosome always being silenced. At the blastocyst stage, the paternal X reactivates and random X inactivation takes place (see Table 1).Although most
%U http://genomebiology.com/2010/11/6/213