Sex reversal following deletion of a single distal enhancer of Sox9

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

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1469-1471
Number of pages3
Issue number6396
Early online date14 Jun 2018
Publication statusPublished - 29 Jun 2018

ASJC Scopus subject areas

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    Gonen, N., Futtner, C. R., Wood, S., Alexandra Garcia-Moreno, S., Salamone, I. M., Samson, S. C., Sekido, R., Poulat, F., Maatouk, D. M., & Lovell-Badge, R. (2018). Sex reversal following deletion of a single distal enhancer of Sox9. Science, 360(6396), 1469-1471.