An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

Highly conserved ribonuclear particles (RNPs) have evolved that target LINE1 (L1) and intracisternal A particle (IAP) transposons for DNA methylation and subsequent epigenetic silencing. In the male germline members of the Piwi subclade of the Argonaute family of proteins, Mili and Miwi2 are essential for de novo DNA methylation of transposons and spermatogenesis. Miwi2 is expressed during a brief window of gonadocyte development that coincides with de novo DNA methylation, whereas Mili has a broad temporal expression window expressed from gonadocytes at E12.5 through most stages of spermatogenesis. Both Mili and Miwi2 bind a class of small non-coding RNAs known as Piwi-interacting RNAs (piRNAs) that are believed to act as guides for targeting of the respective RNPs. One of the major questions we are trying to address is the mechanism by which Miwi2 transduces the piRNA signal that culminates in CpG DNA methylation of L1 and IAP elements.

People contributing to the project:

• Monic DiGiacomo (PostDoc)
• Lina Vasiliauskaite (PhD Student),
• Christian Buch (PhD Student)
• Stefano Comazzetto (PhD Student)