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

Blewitt, M.E., Gendrel, A.V., Pang, Z., Sparrow, D.B., Whitelaw, N., Craig, J.M., Apedaile, A., Hilton, D.J., Dunwoodie, S.L., Brockdorf, N., Kay, G.F. and Whitelaw, E. (2008) SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. Nature Genetics, 40 5: 663-669. doi:10.1038/ng.142


Author Blewitt, M.E.
Gendrel, A.V.
Pang, Z.
Sparrow, D.B.
Whitelaw, N.
Craig, J.M.
Apedaile, A.
Hilton, D.J.
Dunwoodie, S.L.
Brockdorf, N.
Kay, G.F.
Whitelaw, E.
Title SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2008-05-01
Year available 2008
Sub-type Article (original research)
DOI 10.1038/ng.142
Open Access Status
Volume 40
Issue 5
Start page 663
End page 669
Total pages 7
Editor Axton, M.
Place of publication United States
Publisher Nature Publishing Group
Language eng
Subject 920110 Inherited Diseases (incl. Gene Therapy)
110311 Medical Genetics (excl. Cancer Genetics)
C1
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Fri, 17 Apr 2009, 00:20:41 EST by Sarah Elliott on behalf of Royal Brisbane Clinical School