ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation

Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142.
Cell (Impact Factor: 33.12). 07/1989; 57(7):1247-58. DOI: 10.1016/0092-8674(89)90061-5
Source: PubMed

ABSTRACT The ZFX gene on the human X chromosome is structurally similar to the ZFY gene, which may constitute the sex-determining signal on the human Y chromosome. ZFY and ZFX diverged from a common ancestral gene, as evidenced by similarities in their intron/exon organization and exon DNA sequences. The carboxy-terminal exons of ZFY and ZFX both encode 13 zinc fingers; 383 of 393 amino acid residues are identical, and there are no insertions or deletions. Thus, the ZFY and ZFX proteins may bind to the same nucleic acid sequences. ZFY and ZFX are transcribed in a wide variety of XY and (in the case of ZFX) XX cell lines. Transcription analysis of human-rodent hybrid cell lines containing "inactive" human X chromosomes suggests that ZFX escapes X inactivation. This result contradicts the "dosage/X-inactivation" model, which postulated that sex is determined by the total amount of functionally interchangeable ZFY and ZFX proteins.

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Available from: David Page, Jan 13, 2014
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    • "In contrast, homologous DNA sequences that are present on both sex chromosomes, such as amelogenin or zinc finger (ZF) protein coding sequences (Page et al. 1987; Schneider-Gadicke et al. 1989), occur in equimolar amounts (in the heterogametic sex), which in principle should circumvent the issue of unequal copy numbers. Discrimination of sex is then based on either the presence of a sex specific length polymorphism (Bé rubé and Palsbøll 1996; Shaw et al. 2003; Yamamoto et al. 2002) or on restriction fragment length polymorphisms (RFLP, Aasen and Medrano 1990; Amstrup et al. 1993; Palsbøll et al. 1992). "
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    Conservation Genetics 05/2007; 8(3):715-720. DOI:10.1007/s10592-006-9196-8 · 1.85 Impact Factor
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    • "The last exon of ZFX/ZFY, located most proximal to the centromere of four conserved segments and encoding 13 zinc-finger domains, is highly homologous among placental mammals, where ZFX has been shown to escape X-inactivation (Page et al . 1987; Schneider-Gadicke et al . 1989; Jegalian & Page 1998)."
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    ABSTRACT: Sequence polymorphism of homologues ZFX and ZFY, in a 604-base pair exon region, was examined in 10 known males and 10 known females across seven cetacean families and used to design a simple, highly sensitive and widely applicable fluorescent 5' exonuclease assay for gender determination in cetaceans. Multiplex amplification, cloning, and sequencing of these previously uncharacterized regions revealed (i) eight fixed differences between ZFX and ZFY, (ii) 29 variable sites between ZFX and ZFY and (iii) very low interspecific nucleotide diversity for both ZFX and ZFY across all families examined. We developed a 5' exonuclease assay that produces a small (105 bp) polymerase chain reaction (PCR) product from both the X and the Y chromosome orthologs, and used double-labelled fluorescent probes to distinguish between the two genes in a real-time PCR assay that is highly reproducible and sensitive. We demonstrated sex specificity for 33 cetacean species in nine families. Given the availability of conserved primers and sequence information for many mammalian species, this approach to designing sexing assays for a wide range of species is both practical and efficient.
    Molecular Ecology 10/2005; 14(10):3275-86. DOI:10.1111/j.1365-294X.2005.02651.x · 5.84 Impact Factor
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    • "Results larger escape domain in human (Schneider-Gadicke et al., 1989; Adler et al., 1991; Ashworth et al., 1991). Eif2s3x/EIF2S3 have a dense CpG island and encode Escape Domains Differ between Mouse and Human translation initiation and elongation factors (http://www. "
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    ABSTRACT: Escape from X inactivation results in expression of genes embedded within inactive chromatin, suggesting the existence of boundary elements between domains. We report that the 5' end of Jarid1c, a mouse escape gene adjacent to an inactivated gene, binds CTCF, displays high levels of histone H3 acetylation, and functions as a CTCF-dependent chromatin insulator. CpG island methylation at Jarid1c was very low during development and virtually absent at the CTCF sites, signifying that CTCF may influence DNA methylation and chromatin modifications. CTCF binding sites were also present at the 5' end of two other escape genes, mouse Eif2s3x and human EIF2S3, each adjacent to an inactivated gene, but not at genes embedded within large escape domains. Thus, CTCF was specifically bound to transition regions, suggesting a role in maintaining both X inactivation and escape domains. Furthermore, the evolution of X chromosome domains appears to be associated with repositioning of chromatin boundary elements.
    Developmental Cell 02/2005; 8(1):31-42. DOI:10.1016/j.devcel.2004.10.018 · 10.37 Impact Factor
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