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- Title
SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation.
- Authors
Blewitt, Marnie E; Gendrel, Anne-Valerie; Pang, Zhenyi; Sparrow, Duncan B; Whitelaw, Nadia; Craig, Jeffrey M; Apedaile, Anwyn; Hilton, Douglas J; Dunwoodie, Sally L; Brockdorff, Neil; Kay, Graham F; Whitelaw, Emma
- Abstract
X-chromosome inactivation is the mammalian dosage compensation mechanism by which transcription of X-linked genes is equalized between females and males. In an N-ethyl-N-nitrosourea (ENU) mutagenesis screen on mice for modifiers of epigenetic reprogramming, we identified the MommeD1 (modifier of murine metastable epialleles) mutation as a semidominant suppressor of variegation. MommeD1 shows homozygous female-specific mid-gestation lethality and hypomethylation of the X-linked gene Hprt1, suggestive of a defect in X inactivation. Here we report that the causative point mutation lies in a previously uncharacterized gene, Smchd1 (structural maintenance of chromosomes hinge domain containing 1). We find that 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.
- Publication
Nature genetics, 2008, Vol 40, Issue 5, p663
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.142