Transposable Elements (TEs) represent 15% of D. melanogaster genome and many families are still active. TEs expression and insertion is particularly deleterious in the germline since mutations are transmitted to the progeny. Most often TEs over-expression induces sterility in fruit flies. Fortunately, the genome has its own immune system based on small non-coding RNAs targeting TEs by sequence complementarity: piRNAs and siRNAs. Associated with Piwi family proteins, they inhibit TEs expression at the transcriptional or post-transcriptional level. Although the role of epigenetic marks such as H3K9me3 in TEs silencing and piRNAs expression has been extensively documented, little is known about the use of histone variants to control TEs expression.

Histone variants strongly impact nucleosome accessibility, playing important functions in eukaryotic genome regulation: transcription control, DNA repair, cell division, ... Interestingly, while mammals have up to 10 H2A variants with different functions, D. melanogaster has only one, called H2Av. It is known to regulate transcription, to deposit heterochromatin and to mark sites of DNA double-strand breaks when phosphorylated.

In the lab, we have uncovered a role for H2Av in oogenesis, since its depletion leads to a developmental delay, oogenesis arrest and sterility. Moreover, TEs (such as I-element, Max-element and gypsy12) are highly expressed in H2Av mutants and the nuage, known as the “piRNA factory”, does not assemble. Finally, we show that H2Av germline mutants accumulate replication stress and activate DNA damage checkpoints upstream of p53, leading to oogenesis arrest.

Altogether, we have evidences of a new role of H2Av in the defense and maintenance of D. melanogaster genome integrity in the germline, by controlling TEs expression.