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SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation


Blewitt, ME; Gendrel, AV; Pang, ZY; Sparrow, DB; Whitelaw, N; Craig, JM; Apedaile, A; Hilton, DJ; Dunwoodie, SL; Brockdorff, N; Kay, GF; Whitelaw, E
2008-05
NATURE GENETICS
Journal Article
40
5
663-669
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(1). 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.
NATURE PUBLISHING GROUP
TROPHOBLAST GIANT-CELLS; DOSAGE COMPENSATION; CONDENSIN SUBUNIT; MOUSE; GENE; METHYLATION; DNA; PROTEIN; DEFICIENT; COMPLEX
10.1038/ng.142
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Creation Date 2008-05-01 12:00:00