XX mouse cell instability explained

Study suggests XX murine stem cells are under-methylated, shedding light on X chromosome activation

Charles Choi(cqchoi@nasw.org)
Oct 23, 2005

Possessing two X chromosomes can significantly reduce DNA methylation in mouse embryonic stem cells, potentially explaining why such cell lines have proven unstable in culture, scientists report online in Nature Genetics. These findings could also shed light on what genes are involved in X chromosome inactivation and why such inactivation happens, co-author Neil Brockdorff at Hammersmith Hospital in London, UK told The Scientist.

These findings suggest an embryo's sex could have subtle but significant consequences on "diseases where epigenetics plays a difference," Brockdorff said. Uncovering the human homologs of the mouse genes responsible for this reduced methylation could illuminate differences between the species in X inactivation, he added.

In mammals, methylation typically occurs on cytosine residues of CpG dinucleotides. In mice, phosphorimager analysis showed roughly 70 percent of CpG dinucleotides were methylated in two different XY embryonic stem cell lines and in XY and XX somatic cells....

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