Journal article

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

Marnie E Blewitt, Anne-Valerie Gendrel, Zhenyi Pang, Duncan B Sparrow, Nadia Whitelaw, Jeffrey M Craig, Anwyn Apedaile, Douglas J Hilton, Sally L Dunwoodie, Neil Brockdorff, Graham F Kay, Emma Whitelaw

Nature Genetics | NATURE PUBLISHING GROUP | Published : 2008

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)..

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