Synergistic Effect of SRY and Its Direct Target, WDR5, on Sox9 Expression

Abstract

SRY is a sex-determining gene that encodes a transcription factor, which triggers male development in most mammals. The molecular mechanism of SRY action in testis determination is, however, poorly understood. In this study, we demonstrate that WDR5, which encodes a WD-40 repeat protein, is a direct target of SRY. EMSA experiments and ChIP assays showed that SRY could bind to the WDR5 gene promoter directly. Overexpression of SRY in LNCaP cells significantly increased WDR5 expression concurrent with histone H3K4 methylation on the WDR5 promoter. To specifically address whether SRY contributes to WDR5 regulation, we introduced a 4-hydroxy-tamoxifen-inducible SRY allele into LNCaP cells. Conditional SRY expression triggered enrichment of SRY on the WDR5 promoter resulting in induction of WDR5 transcription. We found that WDR5 was self regulating through a positive feedback loop. WDR5 and SRY interacted and were colocalized in cells. In addition, the interaction of WDR5 with SRY resulted in activation of Sox9 while repressing the expression of β-catenin. These results suggest that, in conjunction with SRY, WDR5 plays an important role in sex determination.

Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor

“…Alternatively, decreased Gdf5 (20) and Wdr5 (26) expression, as observed in the transgenic growth plates, may also lead to downregulation of chondrocytic Sox9 expression. Recent studies have reported that WDR5 represses ␤-catenin levels (26). The highly restricted spatial distribution of the PTH2R that we observed in situ within the newborn growth plate, the increased expression of Mmp13 (3, 10) that follows PTH2R overexpression in vivo and TIP39 activation in vitro, and the decreased collagen type II immunostaining in situ implicate a role for this signaling system in the formation of the SOCs at the epiphyseal ends of the cartilaginous anlage.…”

The dual roles of Armigeres subalbatus prophenoloxidase V in parasite melanization and egg chorion melanization in the mosquito Ar. subalbatus

“…subalbatus. SRY is a sex-determining gene, which encodes a transcription factor to trigger male development in most mammals (Berta et al, 1990;Xu et al, 2012), which is a member of the Sox (SRY-like box) gene family of DNA-binding proteins. In arthropod model organism, D. melanogaster, Sox genes are expressed in the brain, developing eye, hindgut, nervous system and testes.…”

Non-chimerism and chimerism pseudo dicentric Y chromosome: two case reports about azoospermia and cytogenetic/molecular genetic analysis in the Chinese population

“…Sinclair et al discovered the SRY in 1990 and they considered that SRY is the best candidate gene for the TDF [14]. Lots of studies have shown that the proteins encoded by the SRY gene play a crucial role in sex determination and differentiation [15][16][17]. DNA hybridization experiments have shown that a single hybridization band of SRY can appear in humans, chimpanzees, and some other male mammals, but does not appear in female animals.…”