Piwi suppresses transcription of Brahma-dependent transposons via Maelstrom in ovarian somatic cells

Abstract

Drosophila Piwi associates with PIWI-interacting RNAs (piRNAs) and represses transposons transcriptionally through heterochromatinization; however, this process is poorly understood. Here, we identify Brahma (Brm), the core adenosine triphosphatase of the SWI/SNF chromatin remodeling complex, as a new Piwi interactor, and show Brm involvement in activating transcription of Piwi-targeted transposons before silencing. Bioinformatic analyses indicated that Piwi, once bound to target RNAs, reduced the occupancies of SWI/SNF and RNA polymerase II (Pol II) on target loci, abrogating transcription. Artificial piRNA-driven targeting of Piwi to RNA transcripts enhanced repression of Brm-dependent reporters compared with Brm-independent reporters. This was dependent on Piwi cofactors, Gtsf1/Asterix (Gtsf1), Panoramix/Silencio (Panx), and Maelstrom (Mael), but not Eggless/dSetdb (Egg)–mediated H3K9me3 deposition. The λN-box B–mediated tethering of Mael to reporters repressed Brm-dependent genes in the absence of Piwi, Panx, and Gtsf1. We propose that Piwi, via Mael, can rapidly suppress transcription of Brm-dependent genes to facilitate heterochromatin formation.

Rewiring of chromatin state and gene expression by transposable elements

“…In addition, although Maelstrom (Mael) is required for Piwi‐mediated repression of transposon transcription, it is not involved in H3K9me3 (Sienski et al., 2012). It has been shown that Brahma, the core adenosine triphosphatase of the SWI/SNF chromatin remodeling complex, associates with Piwi and Mael and activates target TE expression before silencing occurs (Onishi et al., 2020). Moreover, the SUMO E3 ligase Su(var)2–10, the nucleosome remodeler Mi‐2 with its partner MEP‐1, and the histone deacetylase Rpd3 were shown to be linked to piRNA‐guided co‐transcriptional silencing (Mugat et al., 2020; Ninova et al., 2020), suggesting that the PIWI–piRNA pathway uses various nuclear functions to regulate its targets.…”

piRNA‐ and siRNA‐mediated transcriptional repression in Drosophila , mice, and yeast: new insights and biodiversity

“…If RNA synthesis continued at the regular speed, the transcripts would leave the genome before Piwi could trigger the silencing mode of action. A recent study has shown that Maelstrom (Mael) contributes to this process (Onishi et al, 2020)…”

“…Mael in OSCs resides in the nuclear Piwi complex, and this complex further binds to Brahma (Brm), the core unit of the chromatin remodeler SWItch/Sucrose Non-Fermentable (SWI/SNF) complex (Onishi et al, 2020 (Wilson & Roberts, 2011). Piwi-targeted transposons in cultured OSCs are mostly controlled by SWI/SNF, and Piwi in collaboration with Mael reduces the level of SWI/SNF and RNA Pol II around long terminal repeats (LTRs) of target transposons, resulting in transcriptional attenuation (Onishi et al, 2020) (Fig 1). Piwi tethering by artificial piRNAs also repressed Brm-independent genes, but at a slower speed than Brm-dependent genes.…”

“…This may contribute to the increased rate of "trans-targeting" in organisms other than fission yeast. Moreover, as discussed above, at least in Drosophila, the transcription rate of the Piwi targets is reduced by Mael, or other alternative means, before heterochromatin formation occurs at the target loci (Sienski et al, 2012;Chang et al, 2019;Onishi et al, 2020). Whether or not mice have a similar system remains undetermined.…”

“…Mael in OSCs resides in the nuclear Piwi complex, and this complex further binds to Brahma (Brm), the core unit of the chromatin remodeler SWItch/Sucrose Non‐Fermentable (SWI/SNF) complex (Onishi et al , 2020 ) (Fig 1 ). SWI/SNF relaxes chromatin structures around promoter regions, allowing RNA Pol II to initiate transcription (Wilson & Roberts, 2011 ).…”