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.author Araujo, Fabiano C.
dc.contributor.author Milsted, Amy
dc.contributor.author Watanabe, Ingrid K. M. [UNIFESP]
dc.contributor.author Del Puerto, Helen L.
dc.contributor.author Santos, Robson A. S.
dc.contributor.author Lazar, Jozef
dc.contributor.author Reis, Fernando M.
dc.contributor.author Prokop, Jeremy W.
dc.date.accessioned 2016-01-24T14:40:30Z
dc.date.available 2016-01-24T14:40:30Z
dc.date.issued 2015-05-01
dc.identifier http://dx.doi.org/10.1152/physiolgenomics.00138.2014
dc.identifier.citation Physiological Genomics. Bethesda: Amer Physiological Soc, v. 47, n. 5, p. 177-186, 2015.
dc.identifier.issn 1094-8341
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/39086
dc.description.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 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.sponsorship American Heart Association
dc.description.sponsorship National Institutes of Health Office of the Director
dc.description.sponsorship Brazilian National Institute of Science and Technology in Hormones and Women's Health
dc.description.sponsorship Federal University of Minas Gerais
dc.format.extent 177-186
dc.language.iso eng
dc.publisher Amer Physiological Soc
dc.relation.ispartof Physiological Genomics
dc.rights Acesso restrito
dc.subject renin angiotensin system en
dc.subject hypertension en
dc.subject Sox3 en
dc.subject Sry en
dc.subject sex differences en
dc.title Similarities and differences of X and Y chromosome homologous genes, SRY and SOX3, in regulating the renin-angiotensin system promoters en
dc.type Artigo
dc.contributor.institution Universidade Federal de Minas Gerais (UFMG)
dc.contributor.institution Univ Akron
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Med Coll Wisconsin
dc.description.affiliation Univ Fed Minas Gerais, Sch Med, Natl Inst Sci & Technol Mol Med, Belo Horizonte, MG, Brazil
dc.description.affiliation Univ Fed Minas Gerais, Sch Med, Dept Obstet & Gynecol, Belo Horizonte, MG, Brazil
dc.description.affiliation Univ Akron, Dept Biol, Akron, OH 44325 USA
dc.description.affiliation Universidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.affiliation Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Fisiol & Biofis, Belo Horizonte, MG, Brazil
dc.description.affiliation Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA
dc.description.affiliation Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.sponsorshipID American Heart Association: 11PRE7380033
dc.description.sponsorshipID National Institutes of Health Office of the Director: 1K01ES-025435
dc.identifier.doi 10.1152/physiolgenomics.00138.2014
dc.description.source Web of Science
dc.identifier.wos WOS:000353926600005



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