Conservation analysis of sequences flanking the testis-determining gene Sry in 17 mammalian species

BMC Developmental Biology

Peter Koopman¹  Timothy L. Bailey¹  Christian Larney¹ 

[1] Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD, 4072, Australia

关键词: Gonad;    Testis;    Gene regulation;    Y chromosome;    Sex determination;    SRY;   

Others  :  1231013
DOI  :  10.1186/s12861-015-0085-6

 received in 2015-04-08, accepted in 2015-09-25,  发布年份 2015

【 摘 要 】

Background

Sex determination in mammals requires expression of the Y-linked gene Sry in the bipotential genital ridges of the XY embryo. Even minor delay of the onset of Sry expression can result in XY sex reversal, highlighting the need for accurate gene regulation during sex determination. However, the location of critical regulatory elements remains unknown. Here, we analysed Sry flanking sequences across many species, using newly available genome sequences and computational tools, to better understand Sry’s genomic context and to identify conserved regions predictive of functional roles.

Methods

Flanking sequences from 17 species were analysed using both global and local sequence alignment methods. Multiple motif searches were employed to characterise common motifs in otherwise unconserved sequence.

Results

We identified position-specific conservation of binding motifs for multiple transcription factor families, including GATA binding factors and Oct/Sox dimers. In contrast with the landscape of extremely low sequence conservation around the Sry coding region, our analysis highlighted a strongly conserved interval of ~106 bp within the Sry promoter (which we term the Sry Proximal Conserved Interval, SPCI). We further report that inverted repeats flanking murine Sry are much larger than previously recognised.

Conclusions

The unusually fast pace of sequence drift on the Y chromosome sharpens the likely functional significance of both the SPCI and the identified binding motifs, providing a basis for future studies of the role(s) of these elements in Sry regulation.

【 授权许可】

   
2015 Larney et al.

【 图 表 】

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【 参考文献 】

• [1]Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R. Male development of chromosomally female mice transgenic for Sry. Nature. 1991; 351:117-121.
• [2]Sekido R, Lovell-Badge R. Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature. 2008; 453:930-934.
• [3]Albrecht KH, Eicher EM. Evidence That Sry Is Expressed in Pre-Sertoli Cells and Sertoli and Granulosa Cells Have a Common Precursor. Dev Biol. 2001; 240:92-107.
• [4]Bullejos M, Koopman P. Spatially dynamic expression of Sry in mouse genital ridges. Dev Dyn. 2001; 221:201-205.
• [5]Jeske YWA, Mishina Y, Cohen DR, Behringer RR, Koopman P. Analysis of the role of Amh and Fra1 in the Sry regulatory pathway. Mol Reprod Dev. 1996; 44:153-158.
• [6]Hiramatsu R, Matoba S, Kanai-Azuma M, Tsunekawa N, Katoh-Fukui Y, Kurohmaru M et al.. A Critical Time Window of Sry Action in Gonadal Sex Determination in Mice. Development. 2009; 136:129-138.
• [7]Larney C, Bailey TL, Koopman P. Switching on sex: transcriptional regulation of the testis-determining gene Sry. Development. 2014; 141:2195-2205.
• [8]Hacker A, Capel B, Goodfellow P, Lovell-Badge R. Expression of Sry, the Mouse Sex Determining Gene. Development. 1995; 121:1603-1614.
• [9]Margarit E, Guillén A, Rebordosa C, Vidal-Taboada J, Sánchez M, Ballesta F et al.. Identification of Conserved Potentially Regulatory Sequences of the SRY Gene from 10 Different Species of Mammals. Biochem Biophys Res Commun. 1998; 245:370-377.
• [10]Pilon N, Daneau I, Paradis V, Hamel F, Lussier JG, Viger RS et al.. Porcine SRY Promoter Is a Target for Steroidogenic Factor 1. Biol Reprod. 2003; 68:1098-1106.
• [11]Ross DG, Bowles J, Koopman P, Lehnert S. New insights into SRY regulation through identification of 5’ conserved sequences. BMC Mol Biol. 2008; 9:85. BioMed Central Full Text
• [12]Veitia RA, Fellous M, McElreavey K. Conservation of Y chromosome-specific sequences immediately 5′ to the testis determining gene in primates. Gene. 1997; 199:63-70.
• [13]Hughes JF, Rozen S. Genomics and Genetics of Human and Primate Y Chromosomes. Annu Rev Genomics Hum Genet. 2012; 13:83-108.
• [14]Hughes JF, Skaletsky H, Brown LG, Pyntikova T, Graves T, Fulton RS et al.. Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes. Nature. 2012; 483:82-86.
• [15]Prokop JW, Underwood AC, Turner ME, Miller N, Pietrzak D, Scott S et al.. Analysis of Sry duplications on the Rattus norvegicus Y-chromosome. BMC Genomics. 2013; 14:792. BioMed Central Full Text
• [16]Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004; 32:1792-1797.
• [17]Hubisz MJ, Pollard KS, Siepel A. PHAST and RPHAST: phylogenetic analysis with space/time models. Brief Bioinform. 2011; 12:41-51.
• [18]Foster JW, Graves JA. An SRY-Related Sequence on the Marsupial X Chromosome: Implications for the Evolution of the Mammalian Testis-Determining Gene. Proc Natl Acad Sci. 1994; 91:1927-1931.
• [19]Gubbay J, Vivian N, Economou A, Jackson D, Goodfellow P, Lovell-Badge R. Inverted Repeat Structure of the Sry Locus in Mice. Proc Natl Acad Sci. 1992; 89:7953-7957.
• [20]Smit A, Hubley R, Green P. RepeatMasker Open-3.0. 1996.
• [21]Grant CE, Bailey TL, Noble WS. FIMO: scanning for occurrences of a given motif. Bioinformatics. 2011; 27:1017-1018.
• [22]Miyamoto Y, Taniguchi H, Hamel F, Silversides DW, Viger RS. A GATA4/WT1 cooperation regulates transcription of genes required for mammalian sex determination and differentiation. BMC Mol Biol. 2008; 9:44. BioMed Central Full Text
• [23]Bailey TL, Machanick P. Inferring direct DNA binding from ChIP-seq. Nucleic Acids Res. 2012; 40:e128-e128.
• [24]Tevosian SG, Albrecht KH, Crispino JD, Fujiwara Y, Eicher EM, Orkin SH. Gonadal Differentiation, Sex Determination and Normal Sry Expression in Mice Require Direct Interaction Between Transcription Partners GATA4 and FOG2. Development. 2002; 129:4627-4634.
• [25]Gierl MS, Gruhn WH, von Seggern A, Maltry N, Niehrs C. GADD45G Functions in Male Sex Determination by Promoting p38 Signaling and Sry Expression. Dev Cell. 2012; 23:1032-1042.
• [26]Pavesi G, Zambelli F, Pesole G. WeederH: an algorithm for finding conserved regulatory motifs and regions in homologous sequences. BMC Bioinf. 2007; 8:46. BioMed Central Full Text
• [27]Van den Driesche S, Walker M, McKinnell C, Scott HM, Eddie SL, Mitchell RT et al.. Proposed Role for COUP-TFII in Regulating Fetal Leydig Cell Steroidogenesis Perturbation of Which Leads to Masculinization Disorders in Rodents. PLoS ONE. 2012; 7:e37064.
• [28]Gladden JM, Meyer BJ. A ONECUT Homeodomain Protein Communicates X Chromosome Dose to Specify Caenorhabditis elegans Sexual Fate by Repressing a Sex Switch Gene. Genetics. 2007; 177:1621-1637.
• [29]Åkerfelt M, Vihervaara A, Laiho A, Conter A, Christians ES, Sistonen L et al.. Heat Shock Transcription Factor 1 Localizes to Sex Chromatin during Meiotic Repression. J Biol Chem. 2010; 285:34469-34476.
• [30]He Y, Luo M, Yi M, Sheng Y, Cheng Y, Zhou R et al.. Identification of a Testis-Enriched Heat Shock Protein and Fourteen Members of Hsp70 Family in the Swamp Eel. PLoS One. 2013; 8:e65269.
• [31]Desclozeaux M, Poulat F, de Santa BP, Soullier S, Jay P, Berta P et al.. Characterization of two Sp1 binding sites of the human sex determining SRY promoter. Biochim Biophys Acta BBA - Gene Struct Expr. 1998; 1397:247-252.
• [32]De Santa BP, Méjean C, Moniot B, Malclès M-H, Berta P, Boizet-Bonhoure B. Steroidogenic Factor-1 Contributes to the Cyclic-Adenosine Monophosphate Down-Regulation of Human SRY Gene Expression. Biol Reprod. 2001; 64:775-783.
• [33]Sawaya S, Bagshaw A, Buschiazzo E, Kumar P, Chowdhury S, Black MA et al.. Microsatellite Tandem Repeats Are Abundant in Human Promoters and Are Associated with Regulatory Elements. PLoS One. 2013; 8:e54710.
• [34]Yanez-Cuna JO, Arnold CD, Stampfel G, Boryn LM, Gerlach D, Rath M et al.. Dissection of thousands of cell type-specific enhancers identifies dinucleotide repeat motifs as general enhancer features. Genome Res. 2014; 24(7):1147-56.
• [35]Nishino K, Hattori N, Tanaka S, Shiota K. DNA Methylation-Mediated Control of Sry Gene Expression in Mouse Gonadal Development. J Biol Chem. 2004; 279:22306-22313.
• [36]Nishino K, Hattori N, Sato S, Arai Y, Tanaka S, Nagy A et al.. Non-CpG Methylation Occurs in the Regulatory Region of the Sry Gene. J Reprod Dev. 2011; 57:586-593.
• [37]Katoh-Fukui Y, Miyabayashi K, Komatsu T, Owaki A, Baba T, Shima Y et al.. Cbx2, a Polycomb Group Gene, Is Required for Sry Gene Expression in Mice. Endocrinology. 2012; 153:913-924.
• [38]Kuroki S, Matoba S, Akiyoshi M, Matsumura Y, Miyachi H, Mise N et al.. Epigenetic Regulation of Mouse Sex Determination by the Histone Demethylase Jmjd1a. Science. 2013; 341:1106-1109.
• [39]Hossain A, Saunders GF. The Human Sex-Determining Gene SRY Is a Direct Target of WT1. J Biol Chem. 2001; 276:16817-16823.
• [40]Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F et al.. One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering. Cell. 2013; 153:910-918.
• [41]R: A Language and Environment for Statistical Computing. 2014.
• [42]Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S et al.. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004; 5:R80. BioMed Central Full Text
• [43]Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0. Mol Biol Evol. 2013; 30:2725-2729.
• [44]Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L et al.. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 2009; 37(Web Server):W202-W208.
• [45]Mathelier A, Zhao X, Zhang AW, Parcy F, Worsley-Hunt R, Arenillas DJ et al.. JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles. Nucleic Acids Res. 2014; 42:D142-D147.
• [46]Jolma A, Yan J, Whitington T, Toivonen J, Nitta KR, Rastas P et al.. DNA-Binding Specificities of Human Transcription Factors. Cell. 2013; 152:327-339.
• [47]Newburger DE, Bulyk ML. UniPROBE: an online database of protein binding microarray data on protein-DNA interactions. Nucleic Acids Res. 2009; 37(Database issue):D77-D82.
• [48]McWilliam H, Li W, Uludag M, Squizzato S, Park YM, Buso N et al.. Analysis Tool Web Services from the EMBL-EBI. Nucleic Acids Res. 2013; 41:W597-W600.
• [49]Flatt M, PLT: Reference: Racket. PLT Design Inc.; 2010. http://racket-lang.org/tr1/ Accessed 5 Oct 2015.
• [50]Krumsiek J, Arnold R, Rattei T. Gepard: a rapid and sensitive tool for creating dotplots on genome scale. Bioinformatics. 2007; 23:1026-1028.
• [51]Wickham H: ggplot2: Elegant Graphics for Data Analysis. Springer New York; 2009. https://cran. r-project.org/web/packages/ggplot2/citation.html webcite
• [52]Ge R-L, Cai Q, Shen Y-Y, San A, Ma L, Zhang Y, Yi X, Chen Y, Yang L, Huang Y, He R, Hui Y, Hao M, Li Y, Wang B, Ou X, Xu J, Zhang Y et al.. Draft genome sequence of the Tibetan antelope. Nat Commun. 2013; 4:1858.
• [53]Seim I, Fang X, Xiong Z, Lobanov AV, Huang Z, Ma S et al.. Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii. Nat Commun. 2013; 4:2212.
• [54]Hughes JF, Skaletsky H, Pyntikova T, Minx PJ, Graves T, Rozen S et al.. Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee. Nature. 2005; 437:100-103.
• [55]Elsik CG, Tellam RL, Worley KC. The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution. Science. 2009; 324:522-528.
• [56]Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG et al.. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. 2003; 423:825-837.
• [57]Chinwalla AT, Cook LL, Delehaunty KD, Fewell GA, Fulton LA, Fulton RS et al.. Initial sequencing and comparative analysis of the mouse genome. Nature. 2002; 420:520-562.
• [58]Groenen MAM, Archibald AL, Uenishi H, Tuggle CK, Takeuchi Y, Rothschild MF et al.. Analyses of pig genomes provide insight into porcine demography and evolution. Nature. 2012; 491:393-398.
• [59]Geraldes A, Rambo T, Wing RA, Ferrand N, Nachman MW. Extensive Gene Conversion Drives the Concerted Evolution of Paralogous Copies of the SRY Gene in European Rabbits. Mol Biol Evol. 2010; 27:2437-2440.
• [60]Payen EJ, Cotinot CY. Sequence evolution of SRY gene within Bovidae family. Mamm Genome Off J Int Mamm Genome Soc. 1994; 5:723-725.
• [61]Cho YS, Hu L, Hou H, Lee H, Xu J, Kwon S et al.. The tiger genome and comparative analysis with lion and snow leopard genomes. Nat Commun. 2013; 4:2433.
• [62]Yim H-S, Cho YS, Guang X, Kang SG, Jeong J-Y, Cha S-S et al.. Minke whale genome and aquatic adaptation in cetaceans. Nat Genet. 2014; 46:88-92.