Ago2-Mediated Recruitment of HP1a on Transposable Elements in Drosophila Brain

In Drosophila gonads, transposable elements (TEs) are repressed by Piwi-interacting RNA (piRNA) pathway operating both co-transcriptionally and post-transcriptionally. In the non-gonadal tissues, TEs are mainly repressed by short interfering RNA (siRNA) pathway with Argonaute2 (Ago2) as an effector protein. It is generally assumed that this pathway acts at the post-transcriptional level. However, recent data point to its involvement in the co-transcriptional silencing. Here, using DamID, we found drastic decrease of HP1a on TEs (especially on the LTR-containing retrotransposons) and other heterochromatin regions in Ago2-mutant Drosophila brain. HP1a reduction is accompanied by the increased chromatin accessibility of TEs, indicating their derepression. Consistent with these findings, several LTR-containing retrotransposons were up-regulated in larval brain upon Ago2 mutation. Moreover, upon knock-down of lamin Dm0 in neurons, HP1a was increased predominantly on the same set of TEs that have the reduced HP1a binding upon Ago2 mutation. We hypothesize that, since Ago2 was revealed in the common complex with lamin Dm0, the depletion of the latter may release Ago2 in the nucleoplasm, thus enhancing the recruitment of HP1a on TEs. Our findings support the model that TEs in Drosophila brain are partially silenced through Ago2-mediated recruitment of HP1a. Overall design: DamID-seq