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bioRxiv · 10.64898/2026.05.19.726329

In the Drosophila germline H2Av and Arp6 suppress transposons by driving piRNA pathway expression

Andrasi, N.·Ryon, H. M.·Luo, Y.·Fejes Toth, K.
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Abstract

The spatiotemporal control of transcription and the maintenance of germline genome integrity depend on dynamic chromatin architecture. In Drosophila, the actin-related protein Arp6--a core subunit of the SWR1-like Domino chromatin remodeling complex--mediates the deposition of the histone variant H2Av. Previous studies have established H2Av as a key transcriptional regulator that modulates the +1 nucleosome barrier to promote RNA Polymerase II (Pol II) pause release and productive elongation. Conversely, H2Av is also integral to heterochromatin assembly and gene silencing. Here we demonstrate that Arp6 and H2Av are essential for female fertility and the global repression of transposable elements (TEs) in the Drosophila ovary. Rather than repressing TEs directly, we show that Arp6 and H2Av maintain genomic stability indirectly by driving the transcription of core PIWI-interacting RNA (piRNA) pathway genes. Depletion of either chromatin factor leads to a significant loss of piRNAs and reduced non-canonical transcription of dual-strand piRNA clusters. This defect stems from a failure to express the Rhino-Deadlock-Cutoff (RDC) complex, alongside the downregulation of multiple other piRNA biogenesis factors. Genomic profiling confirms that H2Av acts predominantly as an activating signal at host gene promoters. Upon H2Av or Arp6 depletion, genes that rely on H2Av for their expression exhibit a distinct upstream shift and more precise spatial localization of the Pol II peak at the TSS, indicating an impaired transition from transcription initiation into productive elongation. Together, our findings build upon the known transcriptional activation functions of the Arp6-H2Av axis, revealing that this established chromatin mechanism is critical for licensing piRNA-mediated genome defense and ensuring germline maintenance.

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Andrasi, N., Ryon, H. M., Luo, Y., Fejes Toth, K.. 2026-05-21. In the Drosophila germline H2Av and Arp6 suppress transposons by driving piRNA pathway expression. https://doi.org/10.64898/2026.05.19.726329

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