Post-transcriptional suppression of the pioneer factor Zelda protects the adult Drosophila testis from activation of the ovary program

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Maintenance of somatic sex identity is essential for adult tissue function. In the Drosophila testis, adult somatic stem cells known as cyst stem cells (CySCs) require the transcription factor Chinmo to preserve male identity. Loss of Chinmo leads to reprogramming of CySCs into their ovarian counterparts through induction of the female-specific RNA-binding protein Transformer F (Tra F ), though the underlying mechanism has remained unclear. Here, we identify the pioneer transcription factor Zelda (Zld) as a critical mediator of this sex reversal. In wild-type CySCs, zld mRNA is repressed by microRNAs (miRs), but following Chinmo loss, these miRs are downregulated, allowing zld mRNA to be translated. Zld is necessary for feminization of chinmo -mutant CySCs, and ectopic expression of Zld in wild-type CySCs is sufficient to induce Tra F and drive female reprogramming. Two Zld target genes, qkr58E-2 and Ecdysone receptor ( EcR ), are upregulated in chinmo -mutant CySCs and are normally female-biased in adult gonads. Qkr58E-2 facilitates Tra F production, while EcR promotes female gene expression programs. Zld overexpression feminizes otherwise wild-type CySCs by upregulating EcR, which in turn downregulates the chinmo gene. Strikingly, overexpression of Zld also feminizes adult male adipose tissue by inducing Tra F and downregulating Chinmo, indicating that Zld can override male identity in multiple adult XY tissues. Together, these findings uncover a post-transcriptional mechanism in which miRs-mediated repression of a pioneer factor safeguards male identity and prevents inappropriate activation of the female program in adult somatic cells.
Funding Information
  • National Institute of General Medical Sciences (R01GM085075)
  • National Institute of General Medical Sciences (R35-GM156624)
  • National Institute of General Medical Sciences (R35-GM148241)
  • National Institute of General Medical Sciences (R01-GM063024)
  • National Institute of Child Health and Human Development (R03-HD080158)

This publication has 87 references indexed in Scilit: