Alternative titles; symbols
HGNC Approved Gene Symbol: ZFP42
Cytogenetic location: 4q35.2 Genomic coordinates (GRCh38): 4:187,995,771-188,005,246 (from NCBI)
Hosler et al. (1989) cloned mouse Zfp42, which they called Rex1. The deduced 288-amino acid protein has a calculated molecular mass of 32.3 kD. Rex1 has an N-terminal acidic stretch characteristic of an acidic activator domain, followed by 4 repeats of a C2H2 zinc finger motif. It also has 3 putative phosphorylation sites and a possible N-glycosylation site. Northern blot analysis detected a 1.9-kb transcript in F9 mouse stem cells.
Rogers et al. (1991) found that Rex1 was expressed in the inner cell mass of day-4.5 mouse blastocysts. It was also present in the polar trophoblast of the blastocyst and, a day or so later, in ectoplacental cone and extraembryonic ectoderm of the egg cylinder, which are trophoblast-derived tissues. Rex1 abundance declined as the inner cell mass differentiated into embryonic ectoderm. Rex1 was also expressed in placenta at day 18, the final day of gestation, and in spermatocytes during early spermatogenesis. In developing testis, a sharp rise in Rex1 expression coincided with the onset of meiosis around day 10.
By searching an EST database for sequences similar to mouse Rex1, Henderson et al. (2002) identified human ZFP42, which they called REX1. The deduced mouse and human proteins share a high degree of similarity. RT-PCR analysis showed that REX1 was expressed in undifferentiated H7 human stem cells and in trophoblast-differentiated H7 cells.
Using differential plaque hybridization, Hosler et al. (1989) identified Rex1 among a set of genes downregulated in F9 mouse teratocarcinoma stem cells upon retinoic acid-induced differentiation into parietal endoderm or visceral endoderm.
Rogers et al. (1991) found that expression of Rex1 was downregulated in the D3 mouse embryonic stem cell line upon differentiation using 4 different growth conditions.
Reprogramming of X-chromosome inactivation (Xi) during acquisition of pluripotency is accompanied by repression of XIST (314670), the trigger for Xi, and upregulation of its antisense counterpart, TSIX (300181). Navarro et al. (2010) stated that mouse Rex1 is required for Tsix expression and maintenance of pluripotency. They found that Rex1 bound to each end of the DXPas34 microsatellite within the Tsix promoter. Knockdown studies with mouse embryonic stem cells showed that Rex1 downregulation was associated with Tsix downregulation, loss of activating histone marks, and reduced occupancy of the Tsix transcript by RNA polymerase II (see 180660). Navarro et al. (2010) concluded that REX1 is required for efficient elongation of TSIX and acquisition of pluripotency.
Gontan et al. (2012) identified the pluripotency factor REX1 as a key target of RNF12 (300379) in the mechanism of X-chromosome inactivation. RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout mouse embryonic stem cells show an increased level of Rex1. Using chromatin immunoprecipitation sequencing, Rex1 binding sites were detected in Xist and Tsix regulatory regions. Overexpression of Rex1 in female embryonic stem cells was found to inhibit Xist transcription and X-chromosome inactivation, whereas male Rex1 +/- embryonic stem cells showed ectopic X-chromosome inactivation. From this, Gontan et al. (2012) proposed that RNF12 causes REX1 breakdown through dose-dependent catalysis, thereby representing an important pathway to initiate X-chromosome inactivation. Rex1 and Xist are present only in placental mammals, which points to coevolution of these 2 genes and X-chromosome inactivation.
By genomic sequence analysis, Henderson et al. (2002) mapped the ZFP42 gene to chromosome 4q35.2. They noted that the mouse Zfp42 gene maps to a region of chromosome 8 that shares homology of synteny with human chromosome 4q35.2.
Gontan, C., Achame, E. M., Demmers, J., Barakat, T. S., Rentmeester, E., van IJcken, W., Grootegoed, J. A., Gribnau, J. RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation. Nature 485: 386-390, 2012. [PubMed: 22596162] [Full Text: https://doi.org/10.1038/nature11070]
Henderson, J. K., Draper, J. S., Baillie, H. S., Fishel, S., Thomson, J. A., Moore, H., Andrews, P. W. Preimplantation human embryos and embryonic stem cells show comparable expression of stage-specific embryonic antigens. Stem Cells 20: 329-337, 2002. [PubMed: 12110702] [Full Text: https://doi.org/10.1634/stemcells.20-4-329]
Hosler, B. A., LaRosa, G. J., Grippo, J. F., Gudas, L. J. Expression of REX-1, a gene containing zinc finger motifs, is rapidly reduced by retinoic acid in F9 teratocarcinoma cells. Molec. Cell. Biol. 9: 5623-5629, 1989. [PubMed: 2511439] [Full Text: https://doi.org/10.1128/mcb.9.12.5623-5629.1989]
Navarro, P., Oldfield, A., Legoupi, J., Festuccia, N., Dubois, A., Attia, M., Schoorlemmer, J., Rougeulle, C., Chambers, I., Avner, P. Molecular coupling of Tsix regulation and pluripotency. Nature 468: 457-460, 2010. [PubMed: 21085182] [Full Text: https://doi.org/10.1038/nature09496]
Rogers, M. B., Hosler, B. A., Gudas, L. J. Specific expression of a retinoic acid-regulated, zinc-finger gene, Rex-1, in preimplantation embryos, trophoblast and spermatocytes. Development 113: 815-824, 1991. [PubMed: 1821852] [Full Text: https://doi.org/10.1242/dev.113.3.815]