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

被引:23
作者
Araujo, Fabiano C. [1 ,2 ]
Milsted, Amy [3 ]
Watanabe, Ingrid K. M. [4 ]
Del Puerto, Helen L. [1 ,2 ]
Santos, Robson A. S. [5 ]
Lazar, Jozef [6 ,7 ]
Reis, Fernando M. [1 ,2 ]
Prokop, Jeremy W. [6 ,7 ]
机构
[1] Univ Fed Minas Gerais, Sch Med, Natl Inst Sci & Technol Mol Med, Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Sch Med, Dept Obstet & Gynecol, Belo Horizonte, MG, Brazil
[3] Univ Akron, Dept Biol, Akron, OH 44325 USA
[4] Univ Fed Sao Paulo, Dept Med, Div Nephrol, Sao Paulo, Brazil
[5] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Fisiol & Biofis, Belo Horizonte, MG, Brazil
[6] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA
[7] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
基金
美国国家卫生研究院;
关键词
renin angiotensin system; hypertension; Sox3; Sry; sex differences; ELEVATES BLOOD-PRESSURE; GENDER-DIFFERENCES; HPA-AXIS; SEX DETERMINATION; DISEASE; RAT; HYPERTENSION; PROTEINS; ASSOCIATION; EXPRESSION;
D O I
10.1152/physiolgenomics.00138.2014
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:177 / 186
页数:10
相关论文
共 71 条
[1]   The role of SOX proteins in normal pituitary development [J].
Alatzoglou, Kyriaki S. ;
Kelberman, Daniel ;
Dattani, Mehul T. .
JOURNAL OF ENDOCRINOLOGY, 2009, 200 (03) :245-258
[2]   BASIC LOCAL ALIGNMENT SEARCH TOOL [J].
ALTSCHUL, SF ;
GISH, W ;
MILLER, W ;
MYERS, EW ;
LIPMAN, DJ .
JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (03) :403-410
[3]   Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators [J].
Bellott, Daniel W. ;
Hughes, Jennifer F. ;
Skaletsky, Helen ;
Brown, Laura G. ;
Pyntikova, Tatyana ;
Cho, Ting-Jan ;
Koutseva, Natalia ;
Zaghlul, Sara ;
Graves, Tina ;
Rock, Susie ;
Kremitzki, Colin ;
Fulton, Robert S. ;
Dugan, Shannon ;
Ding, Yan ;
Morton, Donna ;
Khan, Ziad ;
Lewis, Lora ;
Buhay, Christian ;
Wang, Qiaoyan ;
Watt, Jennifer ;
Holder, Michael ;
Lee, Sandy ;
Nazareth, Lynne ;
Rozen, Steve ;
Muzny, Donna M. ;
Warren, Wesley C. ;
Gibbs, Richard A. ;
Wilson, Richard K. ;
Page, David C. .
NATURE, 2014, 508 (7497) :494-+
[4]   GENETIC-EVIDENCE EQUATING SRY AND THE TESTIS-DETERMINING FACTOR [J].
BERTA, P ;
HAWKINS, JR ;
SINCLAIR, AH ;
TAYLOR, A ;
GRIFFITHS, BL ;
GOODFELLOW, PN ;
FELLOUS, M .
NATURE, 1990, 348 (6300) :448-450
[5]  
Bodiga V. L., 2013, ASIAN J NEUROSCI, V2013, DOI [10.1155/2013/102602, DOI 10.1155/2013/102602]
[6]   Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators [J].
Bowles, J ;
Schepers, G ;
Koopman, P .
DEVELOPMENTAL BIOLOGY, 2000, 227 (02) :239-255
[7]   Pregnancy Outcome Following Exposure to Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Antagonists A Systematic Review [J].
Bullo, Marina ;
Tschumi, Sibylle ;
Bucher, Barbara S. ;
Bianchetti, Mario G. ;
Simonetti, Giacomo D. .
HYPERTENSION, 2012, 60 (02) :444-+
[8]   Matlnspector and beyond: promoter analysis based on transcription factor binding sites [J].
Cartharius, K ;
Frech, K ;
Grote, K ;
Klocke, B ;
Haltmeier, M ;
Klingenhoff, A ;
Frisch, M ;
Bayerlein, M ;
Werner, T .
BIOINFORMATICS, 2005, 21 (13) :2933-2942
[9]   Nonclassical Renin-Angiotensin System and Renal Function [J].
Chappell, Mark C. .
COMPREHENSIVE PHYSIOLOGY, 2012, 2 (04) :2733-2752
[10]   Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome [J].
Charchar, Fadi J. ;
Bloomer, Lisa D. S. ;
Barnes, Timothy A. ;
Cowley, Mark J. ;
Nelson, Christopher P. ;
Wang, Yanzhong ;
Denniff, Matthew ;
Debiec, Radoslaw ;
Christofidou, Paraskevi ;
Nankervis, Scott ;
Dominiczak, Anna F. ;
Bani-Mustafa, Ahmed ;
Balmforth, Anthony J. ;
Hall, Alistair S. ;
Erdmann, Jeanette ;
Cambien, Francois ;
Deloukas, Panos ;
Hengstenberg, Christian ;
Packard, Chris ;
Schunkert, Heribert ;
Ouwehand, Willem H. ;
Ford, Ian ;
Goodall, Alison H. ;
Jobling, Mark A. ;
Samani, Nilesh J. ;
Tomaszewski, Maciej .
LANCET, 2012, 379 (9819) :915-922