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Sex reversal following deletion of a single distal enhancer of Sox9

Gonen, N; Futtner, CR; Wood, S; Garcia-Moreno, SA; Salamone, IM; Samson, SC; Sekido, R; ... Lovell-Badge, R; + view all (2018) Sex reversal following deletion of a single distal enhancer of Sox9. Science , 360 (6396) pp. 1469-1473. 10.1126/science.aas9408. Green open access

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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.

Type: Article
Title: Sex reversal following deletion of a single distal enhancer of Sox9
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.aas9408
Publisher version: https://doi.org/10.1126/science.aas9408
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, SRY-RELATED GENE, CAMPOMELIC DYSPLASIA, EXPRESSION, MICE, MUTATIONS, UPSTREAM, IDENTIFY, REGIONS, MOUSE, CELLS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10059532
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