Role of SmcHD1 in establishment of epigenetic states required for the maintenance of the X-inactivated state in mice

X inactivation in mammals is regulated by epigenetic modifications. Functional deficiency of SmcHD1 has been shown to cause derepression of X-inactivated genes in postimplantation female mouse embryos, suggesting a role of SmcHD1 in the maintenance of X inactivation. Here we show that derepression of X-inactivated genes accompanied a local reduction in the enrichment of H3K27me3 in MEFs deficient for SmcHD1. Furthermore, many of these genes overlapped with those having a significantly lower enrichment of H3K27me3 at the blastocyst stage in wild-type. Intriguingly, however, depletion of SmcHD1 did not compromise the X-inactivated state in immortalized female MEFs, in which X inactivation had been established and maintained. Taking all these findings together, we suggest that SmcHD1 facilitates the incorporation of H3K27me3 and perhaps other epigenetic modifications at gene loci that are silenced even with the lower enrichment of H3K27me3 at the early stage of X inactivation. The epigenetic state at these loci would, however, remain as it is at the blastocyst stage in the absence of SmcHD1 after implantation, which would eventually compromise the maintenance of the X-inactivated state at later stages.