Structural Maintenance Of Chromosomes Flexible Hinge Domain Containing Protein 1 (SMCHD1)

SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. X-chromosome inactivation is the mammalian dosage compensation mechanism by which transcription of X-linked genes is equalized between females and males.MommeD1 shows homozygous female-specific mid-gestation lethality and hypomethylation of the X-linked gene Hprt1, suggestive of a defect in X inactivation.

SmcHD1 is not required for correct Xist expression, but localizes to the inactive X and has a role in the maintenance of X inactivation and the hypermethylation of CpG islands associated with the inactive X. This finding links a group of proteins normally associated with structural aspects of chromosome biology with epigenetic gene silencing.