ArticlePhysiological genomics2015
Similarities and differences of X and Y chromosome homologous genes, SRY and SOX3, in regulating the renin-angiotensin system promoters.
Article in Physiological genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
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- Aging- and gender-related modulation of RAAS: potential implications in COVID-19 disease.Vascular biology (Bristol, England) · 2021Review
- Higher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities.Cardiovascular research · 2020Review
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- Endocrine Significance of SARS-CoV-2's Reliance on ACE2.Endocrinology · 2020Review
- Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19).The Journal of pathology · 2020Review
- Transcriptome analysis of genes related to gonad differentiation and development in Muscovy ducks.BMC genomics · 2020Article
- COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?International journal of molecular sciences · 2020Article
- Putative contributions of the sex chromosome proteins SOX3 and SRY to neurodevelopmental disorders.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2019Article
- Sex differences in youth elite swimming.PloS one · 2019Article
- Characterization of Coding/Noncoding Variants forJournal of the American Society of Nephrology : JASN · 2018Article
- Sex-specific differences in hypertension and associated cardiovascular disease.Nature reviews. Nephrology · 2018Review
- The Y chromosome: a blueprint for men's health?European journal of human genetics : EJHG · 2017Review
- Wnt signaling, a novel pathway regulating blood pressure? State of the art review.Atherosclerosis · 2017Review
- A genomic atlas of human adrenal and gonad development.Wellcome open research · 2017Article
- The phenotypic impact of the male-specific region of chromosome-Y in inbred mating: the role of genetic variants and gene duplications in multiple inbred rat strains.Biology of sex differences · 2016Article
- Chromosome Y genetic variants: impact in animal models and on human disease.Physiological genomics · 2015Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The renin-angiotensin system (RAS) is subject to sex-specific modulation by hormones and gene products. However, sex differences in the balance between the vasoconstrictor/proliferative ACE/ANG II/AT1 axis, and the vasodilator/antiproliferative ACE2/ANG-(1-7)/MAS axis are poorly known. Data in the rat have suggested the male-specific Y-chromosome gene Sry to contribute to balance between these two axes, but why the testis-determining gene has these functions remains unknown. A combination of in silico genetic/protein comparisons, functional luciferase assays for promoters of the human RAS, and RNA-Seq profiling in rat were used to address if regulation of Sry on the RAS is conserved in the homologous X-chromosome gene, Sox3. Both SRY and SOX3 upregulated the promoter of Angiotensinogen (AGT) and downregulated the promoters of ACE2, AT2, and MAS, likely through overlapping mechanisms. The regulation by both SRY and SOX3 on the MAS promoter indicates a cis regulation through multiple SOX binding sites. The Renin (REN) promoter is upregulated by SRY and downregulated by SOX3, likely through trans and cis mechanisms, respectively. Sry transcripts are found in all analyzed male rat tissues including the kidney, while Sox3 transcripts are found only in the brain and testis, suggesting that the primary tissue for renin production (kidney) can only be regulated by SRY and not SOX3. These results suggest that SRY regulation of the RAS is partially shared with its X-chromosome homolog SOX3, but SRY gained a sex-specific control in the kidney for the rate-limiting step of the RAS, potentially resulting in male-specific blood pressure regulation.
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