The pioneer factor Zelda induces male-to-female somatic sex reversal in adult tissues.

UNLABELLED

Somatic sex identity must be maintained throughout adulthood for tissue function. Adult somatic stem cells in the testis (i.e., CySCs) lacking the transcription factor Chinmo are reprogrammed to their ovarian counterparts by induction of female-specific Tra , but this is not mechanistically understood. Pioneer factors play central roles in direct reprogramming, and many upregulated genes in CySCs contain binding sites for the pioneer factor Zelda (Zld). microRNAs repress mRNA in wild type CySCs, but they are downregulated after Chinmo loss, allowing for mRNA translation. Zld depletion from CySCs suppresses feminization, and ectopic Zld induces Tra and feminizes wild-type CySCs. and ( ), direct Zld targets in the embryo, are female-biased in adult gonads and upregulated in CySCs. The RNA-binding protein Qkr58E-2 produces Tra , while EcR promotes female-biased gene expression. Ectopic Zld feminizes adult male adipose tissue, demonstrating that Zld can instruct female and override male identity in adult XY tissues.

HIGHLIGHTS

mRNA is repressed by microRNAs in XY somatic gonadal cells Zld is upregulated in and required for sex reversal of XY cells Zld induces Qkr58E-2 and EcR, which cause Tra and female-biased transcription Zld feminizes XY adipose cells by inducing Tra and downregulating Chinmo.