ArticleBMC molecular biology2008
A GATA4/WT1 cooperation regulates transcription of genes required for mammalian sex determination and differentiation.
Article in BMC molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.
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Who cites it
64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 163 citations in OpenAlex.
- Molecular Basis of Müllerian Agenesis Causing Congenital Uterine Factor Infertility-A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Pathway-based analysis of GWAs data identifies association of sex determination genes with susceptibility to testicular germ cell tumors.Human molecular genetics · 2014Pooled it
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
- Strain-Dependent Functional Variation of a Sex Specific Sox9 Enhancer.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Molecular mechanisms and multi-organ regulatory roles of anti-Müllerian hormone in female reproduction.Communications biology · 2026Review
- Germ cells are essential for testicular morphogenesis and functional reconstruction in a porcine xenograft model.Scientific reports · 2026Article
- Chromatin-Based Control of Mammalian Sex Determination: Integrating Epigenetic and Metabolic Mechanisms.Advances in experimental medicine and biology · 2026Review
- Transcriptome analysis reveals the sex-switching mechanism of juvenile hermaphroditism in silver pomfret (Pampus argenteus).Biology of sex differences · 2025Article
- Anti-Müllerian hormone in PCOS: Molecular regulation and emerging therapeutic strategies.Biomolecules & biomedicine · 2025Review
- Sertoli cells as a hub in testicular development and male reproductive.Frontiers in cell and developmental biology · 2025Review
- Role ofCurrent issues in molecular biology · 2024Review
- A conserved NR5A1-responsive enhancer regulates SRY in testis-determination.Nature communications · 2024Article
- Article
- Testicular differentiation in 46,XX DSD: an overview of genetic causes.Frontiers in endocrinology · 2024Review
- Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review.Frontiers in endocrinology · 2024Review
- High-Throughput Splicing Assays Identify Known and NovelKidney international reports · 2023Article
- Substrain differences in Sry expression at the stage of sex determination in C57BL/6 mouse strains.The Journal of veterinary medical science · 2023Article
- Transgenic Mouse Models to Study the Development and Maintenance of the Adrenal Cortex.International journal of molecular sciences · 2022Review
- Gonadal Sex Differentiation and Ovarian Organogenesis along the Cortical-Medullary Axis in Mammals.International journal of molecular sciences · 2022Review
- Transcriptome analysis of sex-biased gene expression in the spotted-wing Drosophila, Drosophila suzukii (Matsumura).G3 (Bethesda, Md.) · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn mammals, sex determination is genetically controlled. The SRY gene, located on Y chromosome, functions as the dominant genetic switch for testis development. The SRY gene is specifically expressed in a subpopulation of somatic cells (pre-Sertoli cells) of the developing urogenital ridge for a brief period during gonadal differentiation. Despite this tight spatiotemporal expression pattern, the molecular mechanisms that regulate SRY transcription remain poorly understood. Sry expression has been shown to be markedly reduced in transgenic mice harboring a mutant GATA4 protein (a member of the GATA family of transcription factors) disrupted in its ability to interact with its transcriptional partner FOG2, suggesting that GATA4 is involved in SRY gene transcription.
resultsAlthough our results show that GATA4 directly targets the pig SRY promoter, we did not observe similar action on the mouse and human SRY promoters. In the mouse, Wilms' tumor 1 (WT1) is an important regulator of both Sry and Müllerian inhibiting substance (Amh/Mis) expression and in humans, WT1 mutations are associated with abnormalities of sex differentiation. GATA4 transcriptionally cooperated with WT1 on the mouse, pig, and human SRY promoters. Maximal GATA4/WT1 synergism was dependent on WT1 but not GATA4 binding to their consensus regulatory elements in the SRY promoter and required both the zinc finger and C-terminal regions of the GATA4 protein. Although both isoforms of WT1 synergized with GATA4, synergism was stronger with the +KTS rather than the -KTS isoform. WT1/GATA4 synergism was also observed on the AMH promoter. In contrast to SRY, WT1/GATA4 action on the mouse Amh promoter was specific for the -KTS isoform and required both WT1 and GATA4 binding.
conclusionOur data therefore provide new insights into the molecular mechanisms that contribute to the tissue-specific expression of the SRY and AMH genes in both normal development and certain syndromes of abnormal sex differentiation.
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