Authors:
Joo JE, Novakovic B, Cruickshank M, Doyle LW, Craig JM, Saffery R
Authors notes:
European Journal of Human Genetics Online: 1-6.
Keywords:
X chromosome inactivation,monoallelic expression, gene silencing, DNA methylation
Abstract:
The phenomenon of X chromosome inactivation in female mammals is well characterised and remains the archetypal example of dosage compensation via monoallelic expression.
The temporal series of events that culminates in inactive X-specific gene silencing by DNA methylation has revealed a 'patchwork' of gene inactivation along the chromosome, with approximately 15% of genes escaping.
Such genes are therefore potentially subject to sex-specific imbalance between males and females.
Aside from XIST, the non-coding RNA on the X chromosome destined to be inactivated, very little is known about the extent of loci that may be selectively silenced on the active X chromosome (Xa).
Using longitudinal array-based DNA methylation profiling of two human tissues, we have identified specific and widespread active X-specific DNA methylation showing stability over time and across tissues of disparate origin.
Our panel of X-chromosome loci subject to methylation on Xa reflects a potentially novel mechanism for controlling female-specific X inactivation and sex-specific dimorphisms in humans.
Further work is needed to investigate these phenomena.