Sex reversal following deletion of a single distal enhancer of Sox9

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Gonen, Francis | Futtner, Chris | Wood, Francis | Garcia-Moreno, S Alexandra | Salamone, Isabella | Samson, Francis | Sekido, Ryohei | Poulat, Francis | Maatouk, Danielle | Lovell-Badge, Robin

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. Cell fate decisions require appropriate regulation of key genes. Sox9, 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 Sox9 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 Sox9 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.

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