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

33 Citations (Scopus)

Abstract

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
JournalScience
Volume360
Issue number6396
Early online date14 Jun 2018
DOIs
Publication statusPublished - 29 Jun 2018

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Gonads
Genes
Chromatin
Testis
XY female 46
Gene Editing

ASJC Scopus subject areas

  • General

Cite this

Gonen, N., Futtner, C. R., Wood, S., Alexandra Garcia-Moreno, S., Salamone, I. M., Samson, S. C., ... Lovell-Badge, R. (2018). Sex reversal following deletion of a single distal enhancer of Sox9. Science, 360(6396), 1469-1471. https://doi.org/10.1126/science.aas9408

Sex reversal following deletion of a single distal enhancer of Sox9. / Gonen, Nitzan; Futtner, Chris R.; Wood, Sophie; Alexandra Garcia-Moreno, S.; Salamone, Isabella M.; Samson, Shiela C.; Sekido, Ryohei; Poulat, Francis; Maatouk, Danielle M.; Lovell-Badge, Robin.

In: Science, Vol. 360, No. 6396, 29.06.2018, p. 1469-1471.

Research output: Contribution to journalArticle

Gonen, N, Futtner, CR, Wood, S, Alexandra Garcia-Moreno, S, Salamone, IM, Samson, SC, Sekido, R, Poulat, F, Maatouk, DM & Lovell-Badge, R 2018, 'Sex reversal following deletion of a single distal enhancer of Sox9', Science, vol. 360, no. 6396, pp. 1469-1471. https://doi.org/10.1126/science.aas9408
Gonen N, Futtner CR, Wood S, Alexandra Garcia-Moreno S, Salamone IM, Samson SC et al. Sex reversal following deletion of a single distal enhancer of Sox9. Science. 2018 Jun 29;360(6396):1469-1471. https://doi.org/10.1126/science.aas9408
Gonen, Nitzan ; Futtner, Chris R. ; Wood, Sophie ; Alexandra Garcia-Moreno, S. ; Salamone, Isabella M. ; Samson, Shiela C. ; Sekido, Ryohei ; Poulat, Francis ; Maatouk, Danielle M. ; Lovell-Badge, Robin. / Sex reversal following deletion of a single distal enhancer of Sox9. In: Science. 2018 ; Vol. 360, No. 6396. pp. 1469-1471.
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