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Sex reversal following deletion of a single distal enhancer of Sox9
Open accessAbstract
Sox9 regulation during sex determination: Sex determination is regulated by the Sox9 gene. During testis differentiation, this gene is directly targeted by the product of the Y chromosome–encoded gene Sry . The regulatory region of Sox9 is complex, which is typical of genes with multiple roles in development. Gonen et al. find that a single far-upstream 557–base pair element is critical for up-regulating Sox9 . Without it, XY mice develop as females instead of males. The 557–base pair enhancer is conserved, likely to be relevant to human disorders of sex differentiation, and probably essential because it acts early in a time-critical process, and any failure allows ovary-specific factors to dominate. Science , this issue p. 1469
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“it was recently shown that deletion of a relatively weak distal enhancer in the mouse Sox9 sex determination locus leads to sex reversal, while the phenotypic effects of deleting stronger and more proximal Sox9 enhancers are much less pronounced [510].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [510]
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Metadata
- Authors
- Gonen, N., Futtner, C. R., Wood, S., Garcia-Moreno, S. A., Salamone, I. M., Samson, S. C., Sekido, R., Poulat, F., Maatouk, D. M., & Lovell-Badge, R.
- Affiliations
- The Francis Crick Institute (GB)
- Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL 60611, USA.
- Northwestern University (US)
- University of Aberdeen (GB)
- Department of Genetics and Development, Institute of Human Genetics, CNRS-University of Montpellier UMR9002, Montpellier, France.
- Corresponding author
- Maatouk, Danielle M.
- Lovell-Badge, Robin
- ORCID
- Venue
- Science
- Published
- 2018-06-29
- Volume
- 360
- Issue
- 6396
- Pages
- 1469-1473
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6034650
- OpenAlex
- W2808131961
- Cited by
- 235
- References
- 46
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 24 · 2023: 27 · 2022: 42 · 2021: 33 · 2020: 28 · 2019: 32 · 2018: 16
- FWCI
- 16.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Northwestern Medical Faculty Foundation, Inc.
- Francis Crick Institute
- Agence Nationale de la Recherche
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SOX9, sex determination, sex reversal, distal enhancers, SRY, testicular differentiation, XY females, disorders of sex development, gene expression regulation
- MeSH terms
- Animals, Enhancer Elements, Genetic, Female, Gonadal Dysgenesis, 46,XY, Humans, Male, Testis, Conserved Sequence, Sequence Deletion, Sex Determination Processes, Transcription Initiation Site, Mice, Sex-Determining Region Y Protein, SOX9 Transcription Factor
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