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.
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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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