The immortal conflict, taming transposable elements in the germline

Abstract

In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge, the necessity to erase and reset genomic methylation. This is one of the most drastic epigenetic events in mammalian life.  De novo genome methylation re-encodes the epigenome, imprinting and transposable element (TE) silencing. In the male germline piRNA-directed DNA methylation silences young active TEs. This poorly understood but essential process is central to the immortality of the germline. Upon completion of germline reprogramming with the full erasure of genomic methylation TEs become derepressed. PIWI proteins, MILI and MIWI2, and their associated piRNAs neutralize this threat. Firstly, through base complementarity piRNAs guide the PIWI endonuclease MILI to destroy cytoplasmic transposon RNAs. Secondly, antisense TE-derived piRNAs generated from intricate biogenesis pathways act to guide the nuclear PIWI protein MIWI2 to instruct TE DNA methylation by an unknow mechanism. The mechanism by which MIWI2 instructs TE methylation and epigenetic silencing will be presented.