Evidence for epigenetic alterations in Turner syndrome opens up feasibility of new pharmaceutical interventions.

Abstract:

: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).

journal_name

Curr Pharm Des

authors

Rajpathak SN,Deobagkar DD

doi

10.2174/13816128113199990518

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

1778-85

issue

11

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-54312

journal_volume

20

pub_type

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