Hijacking pre-tRNA enables LTR-retrotransposon-initiated constitutive heterochromatin formation [ChIP-Seq]

Although pericentric DNA sequences diverge among different species, they universally retain the highly conserved H3K9 trimethylation (H3K9me3) mark4-6. While H3K9me3-specific methyltransferase was identified more than 30 years ago7,8, how this enzyme is recruited and nucleated at pericentric heterochromatin during Drosophila somatic development remains unknown.

Here, by leveraging a transposition reporter system combined with a genome-wide RNAi screen, we identified the poly-U binding protein Puf68 as an imperative factor in recruiting SUV39H methyltransferase to initiate pericentric heterochromatin formation. The Puf68 protein binds with high affinity to poly-U tracts in pre-tRNAs, forming a Puf68/pre-tRNA complex that subsequently base-pairs with the primer binding site (PBS) of nascent LTR-retrotransposons.