Nucleic Acids Research, Vol 26, Issue 12 2935-2940, Copyright © 1998 by Oxford University Press
AV Tinker and CJ Brown
X chromosome inactivation occurs early in mammalian development to
transcriptionally silence one of the pair of X chromosomes in females. The
XIST RNA, a large untranslated RNA that is expressed solely from the
inactive X chromosome, is implicated in the process of inactivation. As
previous studies have shown that the XIST gene is methylated on the active
X chromosome, we have treated a mouse/human somatic cell hybrid retaining
an active human X chromosome with demethylating agents to determine whether
expression of the human XIST gene could be induced. Stable expression of
XIST was observed after several rounds of demethylation and stability of
XIST expression correlated with the loss of methylation at the three sites
analysed. We conclude that methylation is sufficient to inhibit expression
of the XIST gene in somatic cell hybrids. No loss of expression was
detected for eight other X-linked genes from the active X chromosome that
was expressing XIST , suggesting that additional developmental or species-
specific factors are required for the inactivation process.
ARTICLES
Induction of XIST expression from the human active X chromosome in mouse/human somatic cell hybrids by DNA demethylation
Department of Medical Genetics, University of British Columbia, 6174 University Boulevard, Vancouver, BC V6T 1Z3, Canada.
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