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Zinc finger protein 42 (Gene ZFP42) Homo sapiensThe ZFP42 gene (map locus 4q35.2) product, REX-1/Zfp-42, is a 310 amino acids long (34.7 kDa), YY1 sub-family transcription factor with four closely spaced C2H2-type (krueppel family) Zn-fingers at 188-212, 217-239, 245-269, and 275-299. REX-1/Zfp-42 was initially described as a factor present at high levels in murine F9 teratocarcinoma stem cells (EC). These cells resemble pluripotent stem cells of the inner cell mass (ICM) that differentiate into primitive endoderm (RrE), precursors of extra-embryonic endoderm (ExEn) lineage. PrE subsequently differentiates into visceral endoderm (VE) and parietal endoderm (PE). VE cells form columnar cells that cover the epiblast and contribute to the visceral yolk sac (marker alpha-fetal protein). PE cells migrate along the inner surface of the trophectoderm and form Reichert’s membrane, markers thrombomodulin and laminin B1. Retinoic acid induced differentiation of F9 leads to rapid reduction in levels of REX-1, Hosler BA, et al. (1989). REX-1 is considered a stem cell marker, because it is present in preimplantation embryonic tissues which include both the trophectoderm and inner cell mass (ICM), Henderson JK, et al (2002); in embryonal carcinoma cells (EC) and in embryonic stem (ES) cells. REX-1 is a marker for a subpopulation of undifferentiated ES cells. REX-1 positive cells and REX-1 negative cells can be inter-converted in the presence of leukemia inhibitory factor (LIF). REX-1 positive cells primarily differentiate into primitive ectoderm and support chimera formation; whereas, REX-1 negative cells differentiate into somatic lineages and form chimera poorly, Toyooka Y, et al. (2008). Masui S, et al. (2008) report that REX-1 is not essential for pluripotency in mouse ES cells. They report that REX-1 negative mES cells are defective in differentiation of visceral endoderm. REX-1 is emerging as an important gene in germ cell and undifferentiated cell lineages. REX-1 is found in spermatocytes, Roger, MB, et al. (1991) and primary oocytes during replication and may play a role in meiosis, Kristensen DM, (2008). REX-1 is expressed in undifferentiated mesenchymal stem cells, Lamoury FM, et al. (2006). Roche S, et al. (2007) report that the presence of OCT4, REX-1 and Gata-4, in human mesenchymal stem cells increases their differentiation efficiency towards osteogenic and adipogenic phenotypes. Recently, the expression of REX-1 in normal epithelial tissue cells has been demonstrated. Mongan NP, et al. (2006) have demonstrated expression of REX-1 in normal human epithelial and carcinoma cell cultures, including normal human keratinocytes, prostate epithelial cells (PrEC), lung epithelial cells and various carcinomas including MDA-MB-468 mammary carcinoma, SCC-15 head and neck squamous cell carcinoma, and N-TERA2 human teratocarcinoma cells. REX-1 is present in kidney (renal) parenchymal tissue, but significantly reduced in renal cell carcinoma, Raman JD, et al. (2006). REX-1 is regulated by the pluripotency-regulating genes, SOX-2, OCT4 and Nanog. Nanog binds REX-1 via its C-terminal within the (Nanog-responsive element) -187 to -286 region of the promoter, Shi W. et al. (2006). Sox-2 and OCT4 augment the upregulation of REX-1 by Nanog. OCT-3/4 was identified as a regulator of REX-1, Rosfjord E and Rizzino A. (1994). OCT4 and SOX-2 synergistically co-occupy many gene promoters thru closely linked domains, POU and HMG, respectively. The REX-1 promoter contains an octamer motif (ATTTGCAT) binding site for POU domain family DNA binding proteins, Hosler BA, et al. (1993). OCT-3/4 activates or represses REX-1 depending upon cell environment and involves different OCT-3/4 binding sites (1-35 activation, 61-126 repression), Ben-Shushan E, et al. (1998). Rox-1 has been identified as a repressor of REX-1, Ben-Shushan E, et al. (1998). Both retinoic acid (RA) and cAMP are required to induce differentiation of primitive endoderm into PE and VE by a REX-1-dependent mechanism, Thompson JR and Gudas LJ (2002). Rex-1 is believed to be an inhibitor of the Janus (JAK)/STAT3 pathway, Xu J, et al. (2008). Sigma offers antibodies, shRNAs and other products useful for the study of the Zinc finger protein 42 homolog. References: Ben-Shushan E, et al. (1998) Rex-1, a gene encoding a transcription factor expressed in the early embryo, is regulated via Oct-3/4 and Oct-6 binding to an octamer site and a novel protein, Rox-1, binding to an adjacent site. Mol Cell Biol. 18: 1866-1878. |
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