Similarities and differences of X and Y chromosome homologous genes, SRY and SOX3, in regulating the renin-angiotensin system promoters

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dc.contributor.authorAraujo, Fabiano C.
dc.contributor.authorMilsted, Amy
dc.contributor.authorWatanabe, Ingrid K. M. [UNIFESP]
dc.contributor.authorDel Puerto, Helen L.
dc.contributor.authorSantos, Robson A. S.
dc.contributor.authorLazar, Jozef
dc.contributor.authorReis, Fernando M.
dc.contributor.authorProkop, Jeremy W.
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionUniv Akron
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionMed Coll Wisconsin
dc.date.accessioned2016-01-24T14:40:30Z
dc.date.available2016-01-24T14:40:30Z
dc.date.issued2015-05-01
dc.description.abstractThe 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 malespecific 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.en
dc.description.affiliationUniv Fed Minas Gerais, Sch Med, Natl Inst Sci & Technol Mol Med, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Sch Med, Dept Obstet & Gynecol, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Akron, Dept Biol, Akron, OH 44325 USA
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Fisiol & Biofis, Belo Horizonte, MG, Brazil
dc.description.affiliationMed Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA
dc.description.affiliationMed Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipAmerican Heart Association
dc.description.sponsorshipNational Institutes of Health Office of the Director
dc.description.sponsorshipBrazilian National Institute of Science and Technology in Hormones and Women's Health
dc.description.sponsorshipFederal University of Minas Gerais
dc.description.sponsorshipIDAmerican Heart Association: 11PRE7380033
dc.description.sponsorshipIDNational Institutes of Health Office of the Director: 1K01ES-025435
dc.format.extent177-186
dc.identifierhttp://dx.doi.org/10.1152/physiolgenomics.00138.2014
dc.identifier.citationPhysiological Genomics. Bethesda: Amer Physiological Soc, v. 47, n. 5, p. 177-186, 2015.
dc.identifier.doi10.1152/physiolgenomics.00138.2014
dc.identifier.issn1094-8341
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/39086
dc.identifier.wosWOS:000353926600005
dc.language.isoeng
dc.publisherAmer Physiological Soc
dc.relation.ispartofPhysiological Genomics
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectrenin angiotensin systemen
dc.subjecthypertensionen
dc.subjectSox3en
dc.subjectSryen
dc.subjectsex differencesen
dc.titleSimilarities and differences of X and Y chromosome homologous genes, SRY and SOX3, in regulating the renin-angiotensin system promotersen
dc.typeinfo:eu-repo/semantics/article
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