ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- Cross-Species Sex Identification and Comparative Analysis of theAnimals : an open access journal from MDPI · 2026Article
- Early Gonadal Development and Sex Determination in Mammal.International journal of molecular sciences · 2022Review
- Alternate Roles of Sox Transcription Factors beyond Transcription Initiation.International journal of molecular sciences · 2021Review
- Transcriptional analysis of the multiple Sry genes and developmental program at the onset of testis differentiation in the rat.Biology of sex differences · 2020Article
- Polyglutamine Repeats in Viruses.Molecular neurobiology · 2019Review
- CRISPR/Cas9-mediated knock-in of the murine Y chromosomal Sry gene.The Journal of reproduction and development · 2018Article
- Transposase-mediated gene modulation in the placenta.Placenta · 2017Review
- Reduced Activity of SRY and its Target Enhancer Sox9-TESCO in a Mouse Species with X*Y Sex Reversal.Scientific reports · 2017Article
- Human Sex Determination at the Edge of Ambiguity: INHERITED XY SEX REVERSAL DUE TO ENHANCED UBIQUITINATION AND PROTEASOMAL DEGRADATION OF A MASTER TRANSCRIPTION FACTOR.The Journal of biological chemistry · 2016Article
- Functional characterization of rare FOXP2 variants in neurodevelopmental disorder.Journal of neurodevelopmental disorders · 2016Article
- Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XY(POS) mice.The Journal of veterinary medical science · 2016Article
- FGFR2 mutation in 46,XY sex reversal with craniosynostosis.Human molecular genetics · 2015Article
- Plasticity of gene-regulatory networks controlling sex determination: of masters, slaves, usual suspects, newcomers, and usurpators.EMBO reports · 2015Review
- Unreported intrinsic disorder in proteins: Disorder emergency room.Intrinsically disordered proteins · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.
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