DNA methylation is an important regulatory component which influences phenotypes by modulating gene expression.
Changes in DNA methylation may lead to altered phenotypes and ability of an organism to respond to stress leading to subsequent manifestation
of life style diseases, cancer, etc. The human X chromosome represents a classical model for epigenetic processes governing differential
regulation of homologous chromosomes. X monosomy (45, XO) leads to Turner's syndrome in human with mild to severe phenotypes.
Using a novel cDNA based high throughput approach of assessing genome wide methylation; we have examined the methylation
landscape in human fibroblasts in 45, XO and 46, XX individuals. We report here that as expected methylation of X linked genes is
different in these two situations. It was observed that methylation of several autosomal genes is also affected in this X monosomy state.
Genes involved in bone remodeling, glucose sensitivity and ovarian function appear to be altered in addition to genes involved in epigenetic
regulatory processes. This opens up interesting possibility of misregulation of DNA methylation in the X monosomy state resulting
in altered gene expression and altered phenotypes. This may be one of the reasons for the variance, differential severity and penetrance in
case of Turner’s syndrome. We propose that a systematic analysis of the molecular genetic mechanisms governing this epigenetic regulation
will open up new therapeutic interventions which will certainly help in reducing severity of the disease and help in better management
of X monosomy (Turner’s syndrome).
Keywords: DNA methylation , Turner’s syndrome, epigenetics, altered penetrance and variability, pharmacological interventions, Epigenetic
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Published on: 01 April, 2014
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