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Philippe Berta - One of the best experts on this subject based on the ideXlab platform.

  • The human Testis Determining Factor SRY binds a nuclear Factor containing PDZ protein interaction domains.
    The Journal of biological chemistry, 1997
    Co-Authors: Francis Poulat, P. De Santa Barbara, Marion Desclozeaux, S. Soullier, B. Moniot, N. Bonneaud, Brigitte Boizet, Philippe Berta
    Abstract:

    Abstract The human Y-linked Testis Determining gene SRY encodes a protein with a DNA binding domain from the high mobility group box family. To date, no function has been assigned to amino acid sequences located outside this DNA binding motif. Here, we identify in a yeast two-hybrid screen a PDZ protein termed SIP-1, as an interacting protein with human SRY. In vitro, biochemical analysis, immunoprecipitation experiments, as well as expression of SIP-1 in human embryonic Testis confirm that the two proteins can interact together. Interacting domains were mapped to the C-terminal seven amino acids of SRY and to the PDZ domains of SIP-1, respectively. We hypothesize that SIP-1 could connect SRY to other transcription Factors providing SRY for its missing trans-regulation domain.

  • The human Testis Determining Factor SRY: A new member of the HMG box protein family
    Biochimie, 1994
    Co-Authors: S. Soullier, Francis Poulat, B. Boizet-bonhoure, Bernard Calas, R. Bennes, Frédéric Heitz, Philippe Berta
    Abstract:

    The product of the sex-Determining gene SRY is a member of the HMG box containing protein superfamily. The HMG box is a DNA-binding domain of about 80 amino acids shared by many proteins with diverse functions. It seems that the functions of the full length protein are restricted to the HMG box but their molecular basis remains to be determined. We have summarized here the properties of this binding domain described so far in the literature and, using a synthetic peptide mimicking the DNA binding domain (SRY80), we have confirmed the existence of DNA minor groove contacts with this domain. Using intrinsic fluorescence of the tryptophane, the interaction between SRY80 and the putative target sequence AACAAAT was also quantified. In conclusion, we also consider the possible putative action of SRY to fulfill its role in sex determination.

  • Gene SRY et anomalies de la determination genetique du sexe chez l’homme
    Andrologie, 1992
    Co-Authors: Francis Poulat, Brigitte Boizet, Catherine Gozé, Philippe Berta
    Abstract:

    Normal sexual development in man is the consequence of a complex process. This review focuses on the translation of genedal sex (XX or XY karyotype) into gonadal sex (Testis or ovary). During the last three years attempts to identify and clone the Testis Determining Factor (TDF) have exploited detailed maps of the Y chromosome established by geneticists over the last decade. A candidate gene, named SRY (sex Determining region, Y) located at the tip of the short arm of the Y chromosome, shows many characteristics in common with TDF in that it is the sole element of the Y chromosome required for male development. The discovery of TDF led us to analyse sex-reversed individuals, i.e. XX males and XY females, with the aim of constructing a model for the processes regulating the development of an organ as complex as the Testis. This SRY gene is now the subject of intense molecular biological effort by various groups, effort which we hope will elucidate the mechanism(s) of sex determination. La compréhension des mécanismes de détermination du sexe chez l’homme a franchi une étape importante ces trois dernières années. Le gène SRY, localisé sur le chromosome Y, et seul élément nécessaire de ce chromosome au développement mâle, a ainsi pu être isolé. De nombreux critères permettent aujour ’hui de l’assimiler au facteur TDF (ou „Testis Determining Factor”). Par l’étude des propriétés de la protéine SRY et par l’étude d’autres formes d’ambiguités sexuelles, on espère aujourd’hui pouvoir progresser dans la reconstitution de la cascade conduisant à la formation d’un organe aussi complexe que le testicule. On conçoit le formidable challenge que cette recherche constitue dans le domaine de la biologie du développement

  • Molecular analysis of the sex-Determining region from the Y chromosome in two patients with Frasier syndrome.
    Hormone research, 1992
    Co-Authors: Philippe Berta, Charles Sultan, D. Morin, F. Poulat, S. Taviaux, J M Lobaccaro, R. Dumas
    Abstract:

    In the Frasier syndrome there is an association between XY gonadal dysgenesis and chronic renal failure. Owing to an observed sex reversal, the Y chromosomes of two girls with this syndrome have been analyzed. Using molecular-biology techniques, no major alterations of the known sex-Determining area of the Y chromosome were found. Furthermore, the sequence did not reveal impairment of the recently described Testis-Determining Factor SRY. These data suggest that in the Frasier syndrome, XY sex reversal and renal failure could be the result of either faulty gene(s) located downstream in the sex differentiation pathway during embryogenesis, or impaired SRY regulation. Preliminary results on the Wilms' tumor suppressor gene WT1, a candidate for acting downstream to SRY, are also provided.

  • Gene SRY et anomalies de la determination genetique du sexe chez l’homme
    Andrologie, 1992
    Co-Authors: Francis Poulat, Brigitte Boizet, Catherine Gozé, Philippe Berta
    Abstract:

    La comprehension des mecanismes de determination du sexe chez l’homme a franchi une etape importante ces trois dernieres annees. Le gene SRY, localise sur le chromosome Y, et seul element necessaire de ce chromosome au developpement mâle, a ainsi pu etre isole. De nombreux criteres permettent aujour ’hui de l’assimiler au facteur TDF (ou „Testis Determining Factor”). Par l’etude des proprietes de la proteine SRY et par l’etude d’autres formes d’ambiguites sexuelles, on espere aujourd’hui pouvoir progresser dans la reconstitution de la cascade conduisant a la formation d’un organe aussi complexe que le testicule. On concoit le formidable challenge que cette recherche constitue dans le domaine de la biologie du developpement

Eric Vilain - One of the best experts on this subject based on the ideXlab platform.

  • Sex Reversal in Humans
    2016
    Co-Authors: Rafael B. Elejalde, Eric Vilain
    Abstract:

    Wnt-4, a member of the Wnt family of locally acting secreted growth Factors, is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups. Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans. In this article, we show that, in testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the Testis-Determining Factor, Sry. Furthermore, we elucidate a possible mechanism for human XY sex reversal associated with a 1p31-p35 duplication including WNT-4. Overexpression of WNT-4 leads to up-regulation of DAX1, which results in an XY female phenotype. Thus, WNT-4, a novel sex-Determining gene, and DAX1 play a concerted role in both the control of female development and the prevention of testes formation. These observations suggest that mammalian sex determination is sensitive to dosage, at multiple steps in its pathway

  • the human Testis Determining Factor sry localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolism
    Journal of Neurochemistry, 2012
    Co-Authors: Daniel Peter Czech, Eric Vilain, Vincent R. Harley, Joohyung Lee, Helena Yin Yee Sim, Clare L. Parish
    Abstract:

    The male gender is determined by the sex-Determining region on the Y chromosome (SRY) transcription Factor. The unexpected action of SRY in the control of voluntary movement in male rodents suggests a role in the regulation of dopamine transmission and dopamine-related disorders with gender bias, such as Parkinson's disease. We investigated SRY expression in the human brain and function in vitro. SRY immunoreactivity was detected in the human male, but not female substantia nigra pars compacta, within a sub-population of tyrosine hydroxylase (TH) positive neurons. SRY protein also co-localized with TH positive neurons in the ventral tegmental area, and with GAD-positive neurons in the substantia nigra pars reticulata. Retinoic acid-induced differentiation of human precursor NT2 cells into dopaminergic cells increased expression of TH, NURR1, D2 R and SRY. In the human neuroblastoma cell line, M17, SRY knockdown resulted in a reduction in TH, DDC, DBH and MAO-A expression; enzymes which control dopamine synthesis and metabolism. Conversely, SRY over-expression increased TH, DDC, DBH, D2 R and MAO-A levels, accompanied by increased extracellular dopamine levels. A luciferase assay demonstrated that SRY activated a 4.6 kb 5' upstream regulatory region of the human TH promoter/nigral enhancer. Combined, these results suggest that SRY plays a role as a positive regulator of catecholamine synthesis and metabolism in the human male midbrain. This ancillary genetic mechanism might contribute to gender bias in fight-flight behaviours in men or their increased susceptibility to dopamine disorders, such as Parkinson's disease and schizophrenia.

  • The human Testis‐Determining Factor SRY localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolism
    Journal of neurochemistry, 2012
    Co-Authors: Daniel Peter Czech, Eric Vilain, Joohyung Lee, Helena Yin Yee Sim, Clare L. Parish, Vincent R. Harley
    Abstract:

    The male gender is determined by the sex-Determining region on the Y chromosome (SRY) transcription Factor. The unexpected action of SRY in the control of voluntary movement in male rodents suggests a role in the regulation of dopamine transmission and dopamine-related disorders with gender bias, such as Parkinson's disease. We investigated SRY expression in the human brain and function in vitro. SRY immunoreactivity was detected in the human male, but not female substantia nigra pars compacta, within a sub-population of tyrosine hydroxylase (TH) positive neurons. SRY protein also co-localized with TH positive neurons in the ventral tegmental area, and with GAD-positive neurons in the substantia nigra pars reticulata. Retinoic acid-induced differentiation of human precursor NT2 cells into dopaminergic cells increased expression of TH, NURR1, D2 R and SRY. In the human neuroblastoma cell line, M17, SRY knockdown resulted in a reduction in TH, DDC, DBH and MAO-A expression; enzymes which control dopamine synthesis and metabolism. Conversely, SRY over-expression increased TH, DDC, DBH, D2 R and MAO-A levels, accompanied by increased extracellular dopamine levels. A luciferase assay demonstrated that SRY activated a 4.6 kb 5' upstream regulatory region of the human TH promoter/nigral enhancer. Combined, these results suggest that SRY plays a role as a positive regulator of catecholamine synthesis and metabolism in the human male midbrain. This ancillary genetic mechanism might contribute to gender bias in fight-flight behaviours in men or their increased susceptibility to dopamine disorders, such as Parkinson's disease and schizophrenia.

  • Pathology of 46, XY pure gonadal dysgenesis: absence of Testis differentiation associated with mutations in the Testis-Determining Factor
    Differentiation; research in biological diversity, 1993
    Co-Authors: Eric Vilain, Francis Jaubert, Marc Fellous, Ken Mcelreavey
    Abstract:

    Abstract Individuals with 46, XY pure gonadal dysgenesis present with a completely female phenotype. These individuals develop bilateral streak gonads and have normal Mullerian structures. The apparent absence of testicular tissue in these individuals suggests a mutation in the initial steps of the male sex-Determining pathway. A candidate gene for the primary signal in this pathway was recently cloned (SRY) which encodes a protein with a DNA-binding capacity. In a study of 14 XY females with pure gonadal dysgenesis harbouring SRY, we analysed the histology of the gonads and compared it to the presence or absence of mutations in the SRY open reading frame (SRY-orf). The histological analysis revealed two distinct groups of streak gonads. In the first group, the gonad was composed of exclusively ovarian-like stroma, with sclero-hyaline nodules in some areas. No tubules were observed. The gonads in the second group were composed of undifferentiated stroma harbouring either tubules or a rete structure. This suggests that in the latter group some differentiation (towards Testis formation) has occurred, whereas in the first group ovarian differentiation has been interrupted. Individuals with mutations in the SRY-orf were found to have streak gonads of the first group, whereas most of the remaining XY females without detectable mutation in the SRY-orf had streak gonads belonging to the second group. On the basis of histology, it may be possible to distinguish between mutations in the sex-Determining or sex-differentiation pathways. We suggest that SRY may play a role in rete Testis formation. We also present arguments favouring the mesonephros as the origin of testicular somatic cells in humans.

  • A minority of 46,XX true hermaphrodites are positive for the Y-DNA sequence including SRY.
    Human Genetics, 1992
    Co-Authors: Ken Mcelreavey, Eric Vilain, F. Richaud, Raphaël Rappaport, Nacer Abbas, Stephen Lortat-jacob, Roland Berger, Maryvonne Leconiat, C. Boucekkine, Kiran Kucheria
    Abstract:

    A total of 30 cases of 46,XX true hermaphroditism was analysed for Y-DNA sequences including the recently cloned gene for male Testis-determination SRY. In 3 cases, a portion of the Y chromosome including SRY was present and, in 2 cases, was localised, to Xp22 by in situ hybridisation. Since previous studies have shown that the majority of XX males are generated by an X-Y chromosomal interchange, the Xp22 position of the Yp material suggests that certain cases of hermaphroditism can arise by the same meiotic event. The phenotype in the 3 SRY-positive cases may be caused by X-inactivation resulting in somatic mosaicism of Testis-Determining Factor expression giving rise to both testicular and ovarian tissues. Autosomal or X-linked mutation(s) elsewhere in the sex-Determining pathway may explain the phenotype observed in the remaining 27 SRY-negative cases.

Peter N. Goodfellow - One of the best experts on this subject based on the ideXlab platform.

  • Early step in mammalian sex determination
    Current opinion in genetics & development, 1996
    Co-Authors: Yashin Ramkissoon, Peter N. Goodfellow
    Abstract:

    Since the cloning of the Y-located Testis-Determining Factor, sex Determining region Y (SRY), several other genes have been implicated in the process of mammalian sex determination. Mutations of an SRY-related gene, SRY-related high-mobility group box 9 (SOX9), result in autosomal sex reversal and campomelic dysplasia. The genes Steroidogenic Factor 1 (SF1) and Wilms' tumour 1 (WT1) are required for early gonadal development as well as for the formation of adrenals and kidneys respectively. The gene responsible for adrenal hypoplasia congenita, DAX1, is a candidate for the X-linked dosage sensitive sex reversal gene (DSS).

  • Sex-reversing mutations affect the architecture of SRY-DNA complexes.
    The EMBO journal, 1994
    Co-Authors: Andrea Pontiggia, Peter N. Goodfellow, Robin Lovell-badge, Vincent R. Harley, R. Rimini, Marco Bianchi
    Abstract:

    Abstract The Testis Determining Factor, SRY, is a DNA binding protein that causes a large distortion of its DNA target sites. We have analysed the biochemical properties of the DNA binding domains (HMG-boxes) of mutant SRY proteins from five patients with complete gonadal dysgenesis. The mutant proteins fall into three categories: two bind and bend DNA almost normally, two bind inefficiently but bend DNA normally and one binds DNA with almost normal affinity but produces a different angle. The mutations with moderate effect on complex formation can be transmitted to male progeny, the ones with severe effects on either binding or bending are de novo. The angle induced by SRY depends on the exact DNA sequence and thus adds another level of discrimination in target site recognition. These data suggest that the exact spatial arrangement of the nucleoprotein complex organized by SRY is essential for sex determination.

  • The biochemical role of SRY in sex determination
    Molecular reproduction and development, 1994
    Co-Authors: Vincent R. Harley, Peter N. Goodfellow
    Abstract:

    The human sex-Determining gene on the Y chromosome, termed SRY, has recently been isolated by positional cloning; compelling evidence now exists equating SRY with the Testis-Determining Factor, TDF. The SRY gene product is an HMG box protein whose DNA-binding activity is vital for Testis formation as sex-reversed patients with SRY mutations lack this activity in vitro. The in vivo DNA target for SRY, however, remains elusive. Here, we show, by gel retardation analysis, that SRY recognises specific DNA sequences and that such sequences exist upstream of the AMH promoter, a potential downstream target for SRY. We also describe the DNA bending and cruciform DNA-binding functions of SRY and propose a model for the potential action of SRY in the "HMG-1-rich" mammalian nucleus.

  • A familial mutation in the Testis-Determining gene SRY shared by both sexes
    Human Genetics, 1992
    Co-Authors: Ralf J Jager, Peter N. Goodfellow, Vincent R. Harley, Rudolf A. Pfeiffer, Gerd Scherer
    Abstract:

    A familial mutation in SRY, the gene coding for the Testis-Determining Factor TDF, was identified in an XY female with gonadal dysgenesis, her father, her two brothers and her uncle. The mutation consists of a T to C transition in the region of the SRY gene coding for a protein motif known as the high mobility group (HMG) box, a protein domain known to confer DNA-binding specificity on the SRY protein. This point mutation results in the substitution, at amino acid position 109, of a serine residue for phenylalanine, a conserved aromatic residue in almost all HMG box motifs known. This F109S mutation was not found in 176 male controls. When recombinant wildtype SRY and SRY^F109S mutant protein were tested in vitro for binding to the target site AAC AAAG, no differences in DNA-binding activity were observed. These results imply that the F109S mutation either is a rare neutral sequence variant, or produces an SRY protein with slightly altered in vivo activity, the resulting sex phenotype depending on the genetic back-ground or environmental Factors.

  • Evolution of sex determination and the Y chromosome: SRY -related sequences in marsupials
    Nature, 1992
    Co-Authors: Jamie W. Foster, Gregory K. Hampikian, Andrew H. Sinclair, Peter N. Goodfellow, Francine E. Brennan, Robin Lovell-badge, Lynne Selwood, Marilyn B. Renfree, Desmond W. Cooper, Jennifer A. Marshall Graves
    Abstract:

    IN mammals, Testis determination is under the control of the Testis-Determining Factor borne by the Y chromosome1,2. SRY, a gene cloned from the sex-Determining region of the human Y chromosome, has been equated with the Testis-Determining Factor in man3–5 and mouse6,7. We have used a human SRY probe to identify and clone related genes from the Y chromosome of two marsupial species. Comparisons of eutherian and metatherian Y-located SRY sequences suggest rapid evolution of these genes, especially outside the region encoding the DNA-binding HMG box. The SRY homologues, together with the mouse Ubely homologues8, are the first genes to be identified on the marsupial Y chromosome.

Vincent R. Harley - One of the best experts on this subject based on the ideXlab platform.

  • the human Testis Determining Factor sry localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolism
    Journal of Neurochemistry, 2012
    Co-Authors: Daniel Peter Czech, Eric Vilain, Vincent R. Harley, Joohyung Lee, Helena Yin Yee Sim, Clare L. Parish
    Abstract:

    The male gender is determined by the sex-Determining region on the Y chromosome (SRY) transcription Factor. The unexpected action of SRY in the control of voluntary movement in male rodents suggests a role in the regulation of dopamine transmission and dopamine-related disorders with gender bias, such as Parkinson's disease. We investigated SRY expression in the human brain and function in vitro. SRY immunoreactivity was detected in the human male, but not female substantia nigra pars compacta, within a sub-population of tyrosine hydroxylase (TH) positive neurons. SRY protein also co-localized with TH positive neurons in the ventral tegmental area, and with GAD-positive neurons in the substantia nigra pars reticulata. Retinoic acid-induced differentiation of human precursor NT2 cells into dopaminergic cells increased expression of TH, NURR1, D2 R and SRY. In the human neuroblastoma cell line, M17, SRY knockdown resulted in a reduction in TH, DDC, DBH and MAO-A expression; enzymes which control dopamine synthesis and metabolism. Conversely, SRY over-expression increased TH, DDC, DBH, D2 R and MAO-A levels, accompanied by increased extracellular dopamine levels. A luciferase assay demonstrated that SRY activated a 4.6 kb 5' upstream regulatory region of the human TH promoter/nigral enhancer. Combined, these results suggest that SRY plays a role as a positive regulator of catecholamine synthesis and metabolism in the human male midbrain. This ancillary genetic mechanism might contribute to gender bias in fight-flight behaviours in men or their increased susceptibility to dopamine disorders, such as Parkinson's disease and schizophrenia.

  • The human Testis‐Determining Factor SRY localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolism
    Journal of neurochemistry, 2012
    Co-Authors: Daniel Peter Czech, Eric Vilain, Joohyung Lee, Helena Yin Yee Sim, Clare L. Parish, Vincent R. Harley
    Abstract:

    The male gender is determined by the sex-Determining region on the Y chromosome (SRY) transcription Factor. The unexpected action of SRY in the control of voluntary movement in male rodents suggests a role in the regulation of dopamine transmission and dopamine-related disorders with gender bias, such as Parkinson's disease. We investigated SRY expression in the human brain and function in vitro. SRY immunoreactivity was detected in the human male, but not female substantia nigra pars compacta, within a sub-population of tyrosine hydroxylase (TH) positive neurons. SRY protein also co-localized with TH positive neurons in the ventral tegmental area, and with GAD-positive neurons in the substantia nigra pars reticulata. Retinoic acid-induced differentiation of human precursor NT2 cells into dopaminergic cells increased expression of TH, NURR1, D2 R and SRY. In the human neuroblastoma cell line, M17, SRY knockdown resulted in a reduction in TH, DDC, DBH and MAO-A expression; enzymes which control dopamine synthesis and metabolism. Conversely, SRY over-expression increased TH, DDC, DBH, D2 R and MAO-A levels, accompanied by increased extracellular dopamine levels. A luciferase assay demonstrated that SRY activated a 4.6 kb 5' upstream regulatory region of the human TH promoter/nigral enhancer. Combined, these results suggest that SRY plays a role as a positive regulator of catecholamine synthesis and metabolism in the human male midbrain. This ancillary genetic mechanism might contribute to gender bias in fight-flight behaviours in men or their increased susceptibility to dopamine disorders, such as Parkinson's disease and schizophrenia.

  • Sex-reversing mutations affect the architecture of SRY-DNA complexes.
    The EMBO journal, 1994
    Co-Authors: Andrea Pontiggia, Peter N. Goodfellow, Robin Lovell-badge, Vincent R. Harley, R. Rimini, Marco Bianchi
    Abstract:

    Abstract The Testis Determining Factor, SRY, is a DNA binding protein that causes a large distortion of its DNA target sites. We have analysed the biochemical properties of the DNA binding domains (HMG-boxes) of mutant SRY proteins from five patients with complete gonadal dysgenesis. The mutant proteins fall into three categories: two bind and bend DNA almost normally, two bind inefficiently but bend DNA normally and one binds DNA with almost normal affinity but produces a different angle. The mutations with moderate effect on complex formation can be transmitted to male progeny, the ones with severe effects on either binding or bending are de novo. The angle induced by SRY depends on the exact DNA sequence and thus adds another level of discrimination in target site recognition. These data suggest that the exact spatial arrangement of the nucleoprotein complex organized by SRY is essential for sex determination.

  • The biochemical role of SRY in sex determination
    Molecular reproduction and development, 1994
    Co-Authors: Vincent R. Harley, Peter N. Goodfellow
    Abstract:

    The human sex-Determining gene on the Y chromosome, termed SRY, has recently been isolated by positional cloning; compelling evidence now exists equating SRY with the Testis-Determining Factor, TDF. The SRY gene product is an HMG box protein whose DNA-binding activity is vital for Testis formation as sex-reversed patients with SRY mutations lack this activity in vitro. The in vivo DNA target for SRY, however, remains elusive. Here, we show, by gel retardation analysis, that SRY recognises specific DNA sequences and that such sequences exist upstream of the AMH promoter, a potential downstream target for SRY. We also describe the DNA bending and cruciform DNA-binding functions of SRY and propose a model for the potential action of SRY in the "HMG-1-rich" mammalian nucleus.

  • A familial mutation in the Testis-Determining gene SRY shared by both sexes
    Human Genetics, 1992
    Co-Authors: Ralf J Jager, Peter N. Goodfellow, Vincent R. Harley, Rudolf A. Pfeiffer, Gerd Scherer
    Abstract:

    A familial mutation in SRY, the gene coding for the Testis-Determining Factor TDF, was identified in an XY female with gonadal dysgenesis, her father, her two brothers and her uncle. The mutation consists of a T to C transition in the region of the SRY gene coding for a protein motif known as the high mobility group (HMG) box, a protein domain known to confer DNA-binding specificity on the SRY protein. This point mutation results in the substitution, at amino acid position 109, of a serine residue for phenylalanine, a conserved aromatic residue in almost all HMG box motifs known. This F109S mutation was not found in 176 male controls. When recombinant wildtype SRY and SRY^F109S mutant protein were tested in vitro for binding to the target site AAC AAAG, no differences in DNA-binding activity were observed. These results imply that the F109S mutation either is a rare neutral sequence variant, or produces an SRY protein with slightly altered in vivo activity, the resulting sex phenotype depending on the genetic back-ground or environmental Factors.

Yutaka Nakahori - One of the best experts on this subject based on the ideXlab platform.

  • Proteomics and transcriptome approaches to investigate the mechanism of human sex determination.
    Cell biology international, 2009
    Co-Authors: Youichi Sato, Toshikatsu Shinka, Gang Chen, Hong-tao Yan, Kozue Sakamoto, Ashraf A. Ewis, Hiroyuki Aburatani, Yutaka Nakahori
    Abstract:

    The SRY gene (sex-Determining region on the Y chromosome) was isolated in 1990 and is known as the Testis-Determining Factor on the Y chromosome. The SRY has been considered as a transcription Factor since it contains an HMG box, which functions as a DNA-binding domain. However, a direct target for SRY remains to be identified. We have investigated the function of SRY through proteomics and transcriptome approaches, and by using two stable SRY-overexpressing cell lines (SRY1 and SRY2) in NT2/D1 cells derived from human testicular embryonal cell carcinoma. The results of 2-dimensional gel electrophoresis show that SRY overexpression causes a considerable downregulation of many chaperone proteins. SRY also upregulates laminin, which is important for Sertoli cell differentiation. Additionally, transcriptome analysis shows that SRY overexpression upregulates many zinc finger proteins and downregulates cellular growth Factors with S or G2/M arrest of the cell cycle and inhibition of cellular proliferation.

  • Sex differentiation and sex chromosomes
    Nihon rinsho. Japanese journal of clinical medicine, 2004
    Co-Authors: Toshikatsu Shinka, Yutaka Nakahori
    Abstract:

    The mechanisms for sex differentiation and the genes on the sex chromosomes are varied among different species. For human, SRY is the only Testis-Determining Factor on the Y chromosome and triggers the cascade for male sex-determination. However, even if normal SRY exists, the haploinsufficienty of SOX9 or KTS+ splicing form of WT-1 can cause male-to-female sex reversal. Furthermore, the duplication of the partial region on the X chromosome including DAX-1 gene can also cause male-to-female sex reversal. The sex-Determining system seems to be sensitive for the gene dosage or the gene expression level.

  • Analysis of the Testis-Determining Gene SRY in Patients with XY Gonadal Dysgenesis
    Hormone Research, 1996
    Co-Authors: Osamu Tsutsumi, Yutaka Nakahori, Taku Lida, Yuji Taketani
    Abstract:

    The sex-Determining region of the Y chromosome (SRY) encodes a gene that has many of the properties expected to the Testis-Determining Factor. XY gonadal dysgenesis is characterized by streak gonads i

  • Detection of the Testis Determining Factor in an XX Man
    The Journal of urology, 1993
    Co-Authors: Keiko Fukutani, Yutaka Nakahori, Takahiro Kajiwara, Shigeo Nagafuchi, Yasuo Nakagome
    Abstract:

    An XX male patient was examined for the presence of 25 loci on the Y chromosome. Only 2 loci, the proximal border of the pseudoautosomal region Y and the sex Determining region Y, were detected in this patient. The other 23 loci, including the zinc finger protein Y, were absent. We presume that a crossing over between the X and Y chromosomes occurred at the region proximal to the sex Determining region Y but distal to the zinc finger protein Y during meiosis of the father.