Human active X-specific DNA methylation events showing stability across time and tissues.
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.
Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
Jihoon Eric
JE
Joo
1] Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia [2] Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
Boris
B
Novakovic
Leukaemia and Cancer Research, Telethon Institute for Child Health Research, University of Western Australia, Perth, Western Australia, Australia.
Mark
M
Cruickshank
1] Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia [2] Neonatal Services, Royal Women's Hospital, Parkville, Victoria, Australia [3] Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia.
Lex W
LW
Doyle
1] Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia [2] Early Life Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
Jeffrey M
JM
Craig
1] Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia [2] Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
Richard
R
Saffery
D041321:Chromosomes, Human, X / Q000235:genetics*; D019175:DNA Methylation; D030541:Databases, Genetic; D004303:Dosage Compensation, Genetic; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D056426:Genetic Loci; D006801:Humans; D008297:Male; D022661:RNA, Untranslated / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*
D022661:RNA, Untranslated