Role of non-coding rnas in gene silencing and parental imprinting

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Project objective

Parental imprinting of mammalian genes is an important genetic principl with far-reaching consequences for development and genetic disease. The mechanism of imprinting is not fully understood, but it has been shown that DNA methylation is involved. An intriguing feature is the presence of genes for non-coding RNAs within all imprinted loci examined so far. They are thought to play a role in gene silencing. Here I propose, to develop in vitro tests to study the influence of the H19 non-coding RNA on the methylation pattern and silencing of the Igf2 gene whose in vivo expression is strongly related to the Hl9 expression. This will lead to identification of the putative active site(s) of the Hl9 RNA. Using gene targeting in mouse ES cells, this active site could then be deleted from the endogenous Hl9 gene to investigate its role in vivo. Finally, this will lead to important insights into the mechanism of imprinting, and into disease mechanisms associated with loss of imprinting (the Beckwith-Wiedemann syndrome in this case). This project will give one valuable training in molecular genetics and ES cell manipulation, building on the skills I have gained in my doctoral training.

Original text from CORDIS.

Participants

• The Babraham Institute · CambridgeCoordinatorUnited Kingdom
• Not availableCity levelFrance

Links

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