Female mammalian cells inactivate transcription from one of their X chromosomes 
to equalize gene expression of X-linked genes between males and females. 
Inactivation is a multistep process that involves a large non-coding RNA termed 
XIST, a variety of epigenetic modifications of chromatin, and alterations in 
protein composition such as enrichment of the histone variant macroH2A. We show 
here that inactive X chromosomes are also enriched in a well-characterized 
protein component of the nuclear scaffold, SAF-A. This protein has been 
implicated in chromatin organization, owing to its high specificity for 
scaffold-associated region (SAR)-DNA, in transcriptional regulation, e.g. of 
hormone-regulated genes, owing to its functional interaction with steroid 
receptors, and in RNA processing, owing to its interaction with RNA and 
heterogeneous nuclear ribonucleoprotein (hnRNP) particles. After near complete 
removal of DNA and associated chromatin proteins such as macroH2A, SAF-A remains 
with the "nuclear matrix", still highlighting the former position of inactive X 
chromosomes. Interestingly, the enrichment of SAF-A in the inactive X chromosome 
depends on the RNA binding domain of the protein, the RGG box, raising the 
possibility that interaction of SAF-A with XIST RNA may contribute to the 
silencing of X-linked genes by local changes in nuclear architecture.