Chromosome Y-Specific DNA Is Transferred to the Short Arm of X Chromosome in Human XX Males

Andersson, M; Page, D C; Chapelle, Albert de la

doi:10.1126/science.3738510

Cited by 114 publications

(37 citation statements)

References 25 publications

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“…In XY mice, testis determination is triggered by the transient expression of a single Y-chromosome gene, Sry (sex-determining region on the Y chromosome) whereas in XX females (in the absence of Sry), ovarian development proceeds . The role of SRY as a genetic switch for testis development is exemplified in humans by the identification of 46, XY females carrying mutations in the SRY gene and by 46, XX male patients with a translocation of Y chromosome material including the SRY gene (Andersson et al, 1986). In transgenic mice, overexpression of Sry during embryogenesis in an XX gonad leads to female-to-male sex reversal, confirming the requirement of Sry for testis determination (Koopman et al, 1991).…”

Section: Introductionmentioning

confidence: 87%

Human SRY inhibits β-catenin-mediated transcription

Bernard

Sim

Knower

et al. 2008

The International Journal of Biochemistry & Cell Biology

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In most mammals, sex is determined by the presence or absence of the SRY gene. SRY encodes a DNA binding HMG-box transcription factor which, during embryogenesis, is the initial trigger of testis differentiation from the bipotential gonad, yet its precise mode of function remains unclear. In ovarian development, R-spondin1 and Wnt4 act through the Wnt/β-catenin signaling pathway to regulate TCF-dependent expression of unknown target genes and repress testis development. Conversely, SRY may be necessary to prevent the development of ovaries by inhibiting the action of ovarian-determining genes. We hypothesize that SRY prevents Wnt/β-catenin signaling, thereby inhibiting ovarian development. In HEK293T cells, SRY repressed β-catenin-mediated TCFdependent gene activation in the presence of a specific GSK3β inhibitor or an activated β-catenin mutant, suggesting that SRY inhibits Wnt signaling at the level of β-catenin. Three SRY mutant proteins with nuclear localization defects, encoded by XY male-to-female patients, failed to inhibit β-catenin; surprisingly four SRY sex reversed mutants with defective DNA binding activity showed near wild-type SRY inhibitory activity. Moreover the potent transactivator SRY-VP16 fusion protein also showed wild-type SRY inhibitory activity. Thus SRY inhibition of β-catenin involves neither DNA binding nor transactivation functions of SRY. β-catenin and SRY interact in-vitro and SRY expression triggered β-catenin localization into specific nuclear bodies in NT2/D1 and Hela cells. We conclude that SRY inhibits β-catenin-mediated Wnt signaling by a novel nuclear function of SRY that could be important in sex determination.

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Section: Introductionmentioning

confidence: 87%

Human SRY inhibits β-catenin-mediated transcription

Bernard

Sim

Knower

et al. 2008

The International Journal of Biochemistry & Cell Biology

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“…When specific DNA probes for different regions of the Y chromosome became available, it was shown that most XX males carry some Y DNA material in their genome and that they are a heterogenous group, with variable amounts of Y chromosome material [5][6][7][8]. In our patient, DNA analysis using a panel of Y-specific probes detected several Y chromosome DNA sequences including SRY in a region close to the centromere of the paternal X chromo some.…”

Section: Discussionmentioning

confidence: 90%

Hormonal, Genetic and Clinical Findings in an XX Male

Birnbacher¹,

Frisch²

1995

Horm Res

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A 17-year-old XX male with constitutional delay of growth and development and genetic short stature is described. Testosterone levels were normal but luteinizing-hormone-releasing-hormone-stimulated gonadotropin concentrations were increased. Testicular biopsy showed atrophic tubuli seminiferi and hyperplasia of the Leydig cells, and the spermiogram indicated azoospermia. Molecular analysis demonstrated the SRY gene close to the centromere of the paternally derived X chromosome. Clinical data in addition to the cytogenetic and molecular aspects are discussed.

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“…This is known from study of XX males, who have this portion of the Y chromosome translocated to the X chromosome [Affara et al, 1986;Anderson et al, 1986;Anneren et al, 1987;Guellaen et al, 1984;Muller et al, 1986;Page et al, 1985;Vergnaud et al, 19861 or to an autosome [Schempp et al, 1985;de la Chapelle et al, 1986;Maserati et al, 19861. In addition, individuals lacking most of Yq have male genitalia.…”

Section: Introductionmentioning

confidence: 94%

Interstitial deletion involving most of Yq

et al. 1990

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Males with a Yq deletion are well described, but few have been studied with both cytogenetic and molecular techniques to define the deletion and relate it to the phenotype. This study reports an analysis of cells obtained from a college student with azoospermia, short stature, and a small penis. Cytogenetic analysis indicated that the entire Yq was deleted, but DNA hybridization showed that a portion of Yq12 remained. We conclude that the deletion is interstitial.

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Chromosome Y-Specific DNA Is Transferred to the Short Arm of X Chromosome in Human XX Males

Cited by 114 publications

References 25 publications

Human SRY inhibits β-catenin-mediated transcription

Human SRY inhibits β-catenin-mediated transcription

Hormonal, Genetic and Clinical Findings in an XX Male

Interstitial deletion involving most of Yq

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