Loss of Atrx Affects Trophoblast Development and the Pattern of X-Inactivation in Extraembryonic Tissues

MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
PLoS Genetics (Impact Factor: 8.17). 05/2006; 2(4):e58. DOI: 10.1371/journal.pgen.0020058
Source: PubMed

ATRX belongs to a class of proteins that may modify how DNA is packaged into chromatin, altering the accessibility of other proteins in the nucleus to DNA. In this way, ATRX is thought to influence gene expression. Mutations in the ATRX gene, which is located on the female sex chromosome (X), provided the first example of a human disease (ATR-X syndrome) associated with defects in such proteins. Affected males (XMUTY) have multiple developmental abnormalities in a wide variety of systems. Currently, it is not understood how proteins like ATRX influence cell biology. To address this question, the authors deleted the version of the gene in mice, Atrx. Although affected male mice (XMUTY) started to develop normally, they died early in development because they failed to form a normal placenta. In the placenta, female mice normally inactivate the X chromosome that they inherit from their fathers (Xp), so if females inherit from their mother an X chromosome (Xm) that bears the abnormal copy of Atrx (XmMUTXp), one would predict that, like affected males, they would fail to form a normal placenta. The authors unexpectedly found this not to be so. They showed, instead, that in such females the normal, paternally derived Atrx gene is active. This study has therefore demonstrated an important facet of X-chromosome imprinting.

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