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

Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142.
Cell (Impact Factor: 32.24). 07/1989; 57(7):1247-58. DOI: 10.1016/0092-8674(89)90061-5
Source: PubMed


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 metatherian (marsupial) mammals, genes related to ZFX and ZFY are autosomal (3), and it is thought that ZFX and ZFY originated more than 100 million years ago, after the separation of eutherian and metatherian lineages, by translocation of an autosomal segment to the pseudo-autosomal region in a common ancestor of extant eutherians (4). ZFY and ZFX genes code putative transcription activators, characterized by a large N-terminal acidic (activating) domain (approximately 360 amino acids) and a C-terminal DNA-binding domain of 12–13 Cys2-His2 zinc fingers, separated by a short basic nuclear localization signal (5,6). The DNA targets and protein partners of ZFY and ZFX remain to be determined. "
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    ABSTRACT: Mammalian ZFY genes are located on the Y chromosome, and code putative transcription factors with 12-13 zinc fingers preceded by a large acidic (activating) domain. In mice, there are two genes, Zfy1 and Zfy2, which are expressed mainly in the testis. Their transcription increases in germ cells as they enter meiosis, both are silenced by meiotic sex chromosome inactivation (MSCI) during pachytene, and Zfy2 is strongly reactivated later in spermatids. Recently, we have shown that mouse Zfy2, but not Zfy1, is involved in triggering the apoptotic elimination of specific types of sex chromosomally aberrant spermatocytes. In humans, there is a single widely transcribed ZFY gene, and there is no evidence for a specific role in the testis. Here, we characterize ZFY transcription during spermatogenesis in mice and humans. In mice, we define a variety of Zfy transcripts, among which is a Zfy2 transcript that predominates in spermatids, and a Zfy1 transcript, lacking an exon encoding approximately half of the acidic domain, which predominates prior to MSCI. In humans, we have identified a major testis-specific ZFY transcript that encodes a protein with the same short acidic domain. This represents the first evidence that ZFY has a conserved function during human spermatogenesis. We further show that, in contrast to the full acidic domain, the short domain does not activate transcription in yeast, and we hypothesize that this explains the functional difference observed between Zfy1 and Zfy2 during mouse meiosis.
    Human Molecular Genetics 03/2012; 21(12):2631-45. DOI:10.1093/hmg/dds088 · 6.39 Impact Factor
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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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    ABSTRACT: Extractions from non-invasive hair samples usually yield low amounts of highly degraded DNA. Previously developed mammal molecular sexing methods were not designed with such sub-optimal conditions in mind. We developed a simple and reliable PCR-based sexing method aimed at degraded, low yield DNA extractions from the giant panda (Ailuropoda melanoleuca). Comparisons of this new primer set with others showed that the reliability of sex determination from low-yield, degraded DNA extractions was improved if; amplification products were short (<170bp); and the Y-chromosome amplification product was shorter than the X-chromosome amplification product. The primers developed in this study appear useful for sex determination in other bear species.
    Conservation Genetics 05/2007; 8(3):715-720. DOI:10.1007/s10592-006-9196-8 · 2.19 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 · 6.49 Impact Factor
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