Sex reversal following deletion of a single distal enhancer of Sox9

Journal Article: ScienceYear Published: (2018) Volume Number: 360, Article Number: 1469-1473


Gonen,Nitzan; Futtner,Chris R; Wood,Sophie; Garcia-Moreno,S Alexandra; Salamone,Isabella M; Samson,Shiela C; Sekido,Ryohei; Poulat,Francis; Maatouk,Danielle M; Lovell-Badge,Robin

Cell fate decisions require appropriate regulation of key genes. , a direct target of SRY, is pivotal in mammalian sex determination. In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of Although others are redundant, enhancer 13 (Enh13), a 557-base pair element located 565 kilobases 5' from the transcriptional start site, is essential to initiate mouse testis development; its deletion results in XY females with transcript levels equivalent to those in XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans.