ArticleMolecular and cellular biochemistry2010
The male-determining gene SRY is a hybrid of DGCR8 and SOX3, and is regulated by the transcription factor CP2.
Article in Molecular and cellular biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 54 citations in OpenAlex.
- AMHY and sex determination in egg-laying mammals.Genome biology · 2025Article
- Evolution and regulation of animal sex chromosomes.Nature reviews. Genetics · 2025Review
- RNF4 mediated degradation of PDHA1 promotes colorectal cancer metabolism and metastasis.NPJ precision oncology · 2024Article
- Unraveling the molecular complexity: Wtap/Ythdf1 and Lcn2 in novel traumatic brain injury secondary injury mechanisms.Cell biology and toxicology · 2024Article
- Role ofInternational journal of molecular sciences · 2023Article
- B lymphocytes transdifferentiate into immunosuppressive erythroblast-like cells.Frontiers in immunology · 2023Article
- Evolutionary History of Sexual Differentiation Mechanism in Insects.Molecular biology and evolution · 2022Article
- Evolution of master sex determiners: TGF-β signalling pathways at regulatory crossroads.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2021Review
- Neglected Functions of TFCP2/TFCP2L1/UBP1 Transcription Factors May Offer Valuable Insights into Their Mechanisms of Action.International journal of molecular sciences · 2018Review
- Vertebrate sex determination: evolutionary plasticity of a fundamental switch.Nature reviews. Genetics · 2017Review
- TFCP2 activates beta-catenin/TCF signaling in the progression of pancreatic cancer.Oncotarget · 2017Article
- MicroRNA-144 is regulated by CP2 and decreases COX-2 expression and PGE2 production in mouse ovarian granulosa cells.Cell death & disease · 2017Article
- Genomes of Ellobius species provide insight into the evolutionary dynamics of mammalian sex chromosomes.Genome research · 2016Article
- Plasticity of gene-regulatory networks controlling sex determination: of masters, slaves, usual suspects, newcomers, and usurpators.EMBO reports · 2015Review
- Genomic imprinting, action, and interaction of maternal and fetal genomes.Proceedings of the National Academy of Sciences of the United States of America · 2015Review
- Epigenetic changes in the developing brain: Effects on behavior.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Similarities and differences of X and Y chromosome homologous genes, SRY and SOX3, in regulating the renin-angiotensin system promoters.Physiological genomics · 2015Article
- Structural and functional conservation of fungal MatA and human SRY sex-determining proteins.Nature communications · 2014Article
- Comparative transcriptomics in East African cichlids reveals sex- and species-specific expression and new candidates for sex differentiation in fishes.Genome biology and evolution · 2014Article
- Review
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Authors and funding
5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
In mammals, sex is determined by the presence or absence of the Y chromosome that bears a male-dominant sex-determining gene SRY, which switches the differentiation of gonads into male testes. The molecular signaling mechanism turning on the switch, however, has remained unclear for 18 years since the identification of the gene. Here, we describe how this gene emerged and started to work. From amino acid homology, we realized that SRY is a hybrid gene between a portion of the first exon of DiGeorge syndrome critical region gene 8 (DGCR8) and the high-mobility group (HMG) box of SRY box-3 (SOX3) gene. We identified the regulatory sequence in the SRY promotor region by searching for a common motif shared with DGCR8 mRNA. From the motif search between DGCR8 mRNA and the SRY upstream sequence, we found that the transcription factor CP2 (TFCP2) binding motif is present in both. TFCP2 overexpression did not show a significant increase of SRY mRNA expression, and TFCP2 suppression by RNA interference (RNAi) significantly reduced SRY mRNA expression. Furthermore, electrophoretic mobility shift assay (EMSA) demonstrated that TFCP2 acts as a regulator by directly binding to the SRY promoter. We conclude that SRY is a hybrid gene composed of two genes, DGCR8 and SOX3; and TFCP2 is an essential transcription factor for SRY expression regulation.
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