Smchd1 was identified as a semidominant suppressor of variegation in an ENU mutagenesis screen designed to detect epigenetic modifiers. The ENU derived mutant allele (Smchd1MommeD1) contains a nonsense mutation that causes nonsense mediated decay of Smchd1 transcript. FVB/n background female Smchd1MommeD1/MommeD1 embryos failed at mid-gestation, whereas mutant males were relatively unaffected. This phenotype suggested that Smchd1 was involved in X inactivation and subsequent studies showed that while the inactive X elect was decorated with Xist transcript and H3K27me3, many genes either failed to become inactivated or were re-expressed due to failure of X inactivation. None of the genes tested showed the CpG island hypermethylation characteristic of genes subject to X inactivation. Subsequent studies have shown that not all X-linked genes failed X inactivation in Smchd1 mutants. In order to determine the reason why some genes were still able to undergo X inactivation in Smchd1 mutants, we needed to compile a comprehensive list of the X inactivation status of all genes on X chromosome. We generated mouse embroys carrying polymorphic X chromosomes, an Xist knockout to force total nonrandom X inactivation and the Smchd1 mutation (and relevant control genetypes). Using this model system we undertook genome wide RNA-Seq and MBD-Seq analysis to determine the X inactivation and DNA methylation status of all expressed X-linked genes. The list of genes derived from this analysis will be used to determne whether there are common genomic characteristics that define whether an X-linked gene is dependent on Smchd1 for X inactivation.