Disease relevance of ZFX

• Previous investigations have shown that in other diseases and genes, most notably haemophilia B and A, but also the ZFY and ZFX genes, the male mutation rate for point mutations tends to be higher than the female one [1].
• We have analyzed samples of human prostate adenocarcinoma for the expression of ZFY and ZFX transcripts [2].
• In 2 of the 6 benign prostatic hypertrophy (BPH) tissues analyzed by RT-PCR, barely detectable products of ZFY were observed, and none contained ZFX products [2].
• Two genes with these properties are ZFX and RPS4X, both of which have been proposed to play a role in Turner's syndrome [3].
• ZFX transactivation of the HIV-1 LTR is cell specific and depends on core enhancer and TATA box sequences [4].

High impact information on ZFX

• We report the simultaneous analysis of single cells at five commonly deleted dystrophin exons and at the ZFX/ZFY loci [5].
• ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation [6].
• Transcription analysis of human-rodent hybrid cell lines containing "inactive" human X chromosomes suggests that ZFX escapes X inactivation [6].
• ZFY and ZFX diverged from a common ancestral gene, as evidenced by similarities in their intron/exon organization and exon DNA sequences [6].
• Here, we report that ZFX encodes a protein composed of a highly acidic amino-terminal domain, a basic putative nuclear-localization signal, and a carboxy-terminal zinc-finger domain [7].

Biological context of ZFX

• 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 [6].
• Alternative splicing generates ZFX transcripts encoding isoforms of 575 and 804 amino acids [7].
• We have isolated cDNA clones of ZFY and its homologue on the X chromosome, ZFX [8].
• While autosomal homologs of ZFX have not been observed in other placental mammals, a locus derived from a processed Zfx transcript is found on mouse chromosome 10 band B3 or B4 [9].
• By in situ hybridization, we assigned ZFX and ZFY to human chromosome bands Xp21 and Yp11.3, respectively [10].

Anatomical context of ZFX

• ZFY and ZFX are transcribed in a wide variety of XY and (in the case of ZFX) XX cell lines [6].
• Maternal transcripts for G6PD, ADA, and ZFX were detected in all oocytes and embryos and at all stages [11].
• In contrast, the ZFX gene is expressed as a 5-kb transcript in the testis and as 6.7- and 8-kb transcripts in both ovarian and somatic tissues [12].
• None of the sample blanks showed any PCR product, all 90 of the karyotypically XY cells were correctly genotyped as ZFX/ZFY, all 83 of the 84 XX cells that amplified were correctly genotyped as ZFX only, and analyses of all same-embryo blastomeres were completely concordant (100% specificity) [13].
• Coamplification of the ZFX and ZFY genes for sex identification in preimplantation embryos [14].

Other interactions of ZFX

• The ZFY probe detects a male-specific (Y-linked) sequence in DNA from a range of eutherian mammals, as well as an X-linked sequence (ZFX) which maps to the human X chromosome [15].
• The results also confirm the localization of ZFX distal to POLA (alpha-DNA polymerase) [16].
• As judged by comparative mapping, it appears that an X-chromosomal segment that spans the ZFX and DMD genes has remained grossly intact during the divergence of mouse and human from a common ancestor [9].
• Possible origins of ZFX, ZFY and CMPX1 from a common ancestral gene are discussed [17].
• Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) identified one copy of the zinc finger protein on the X chromosome (ZFX) and two copies of the steroid sulfatase gene (STS), further delineating the breakpoints [18].

Analytical, diagnostic and therapeutic context of ZFX

• Mapping the human ZFX locus to Xp21.3 by in situ hybridization [19].
• The aim of the present study was to find an enzyme which would distinguish sexes in the horse by finding a polymorphic restriction site between the ZFY and ZFX homologues amplified by the polymerase chain reaction (PCR) [20].
• An X-linked zinc finger gene mapping to Xq21.1-q21.3 closely related to ZFX and ZFY: possible origins from a common ancestral gene [17].
• An Alu element insertion in the ZFX intron results in a size difference in the amplicons which is resolved by agarose gel electrophoresis [21].

References