Disease relevance of Zfp42

• Rex-1 is a zinc finger-containing gene that is expressed in embryonal carcinoma (EC) cells and embryonic stem (ES) cells [1].
• In contrast to results in F9 cells, we have been unable thus far to detect REX-1 mRNA in day 7.5 to 12.5 mouse embryo RNA samples or in the P19 teratocarcinoma stem cell line [2].
• CONCLUSIONS: Reduced expression of Cx43 accelerates the onset and increases the incidence, frequency, and duration of ventricular tachyarrhythmias after coronary artery occlusion [3].
• Reduced expression of the nm23 gene in certain rodent model systems and human breast tumors has been correlated with high tumor metastatic potential [4].
• Reduced expression of TSH beta constructs was also found in GH3 and GH4 pituitary tumor lines [5].

High impact information on Zfp42

• Reduced expression of neural cell adhesion molecule induces metastatic dissemination of pancreatic beta tumor cells [6].
• Reduced expression of Met could be related to the extent of tumor cell differentiation [7].
• Selection in L-histidinol or G418 produced clones in which the coding sequences for histidinol-dehydrogenase or neomycin-phosphotransferase were fused to sequences in or near the 5' exons of expressed genes, including one in the developmentally regulated REX-1 gene [8].
• Surface properties of bacillus Calmette-Guérin-activated mouse macrophages. Reduced expression of mannose-specific endocytosis, Fc receptors, and antigen F4/80 accompanies induction of Ia [9].
• Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes [10].

Chemical compound and disease context of Zfp42

• An octamer motif contributes to the expression of the retinoic acid-regulated zinc finger gene Rex-1 (Zfp-42) in F9 teratocarcinoma cells [11].

Biological context of Zfp42

• Human Rex-1 (hRex-1) (also referred to as zinc-finger protein-42, Zfp42) encodes a zinc finger protein expression of which is believed to be characteristic of pluripotent stem cells [12].
• Rex-1 reporter plasmids including this octamer site also exhibited reduced expression in F9 cells treated with RA [11].
• The putative REX-1 protein identified by DNA sequence analysis contains four repeats of the zinc finger nucleic acid-binding motif and a potential acidic activator domain, suggesting that REX-1 encodes a regulatory protein [2].
• A region required for Rex-1 promoter activity in F9 stem cells contains an octamer motif (ATTTGCAT) which is a binding site for octamer transcription factor members of the POU domain family of DNA-binding proteins [11].
• As an initial confirmation of the in vivo relevance of the isolated fragment, a larger Rex-1 promoter fragment, also containing the octamer site, was able to promote expression of the bacterial lacZ gene in mouse embryos at the morula stage [11].

Anatomical context of Zfp42

• Detailed mapping of these genes with Oct4, Rex1 and Fgf5 on pregastrulation embryos provided the first molecular evidence for the existence of successive, temporally distinct pluripotent cell populations in the embryo between the ICM and primitive ectoderm [13].
• RNAi knockdown of Zfp42 induced ES cells differentiate to endoderm and mesoderm lineages, and overexpression of Zfp42 also caused ES cells to lose the capacity of self-renewal [14].
• The fact that these CD34+ cells also express transcription factors (Rex-1 and Oct-4) that are found in early development elicits the hypothesis that they may be pluripotent embryonic-like stem cells [15].
• The only tested adult tissue that contains detectable amounts of Rex-1 mRNA is the testis [16].
• As expected for a stem-cell-specific message, Rex-1 mRNA is present in the inner cell mass (ICM) of the day 4.5 mouse blastocyst [16].

Associations of Zfp42 with chemical compounds

• Upon differentiation with retinoic acid (RA), transcription of the Rex-1 gene decreases rapidly [1].
• Expression of Rex-1 is reduced at the transcriptional level when F9 cells are induced by the addition of retinoic acid (RA) to differentiate [11].
• The REX-1 mRNA decrease did not result from the reduction in cell growth rate associated with the differentiation process, since the REX-1 mRNA level did not decline in F9 cells that were partially growth arrested after 48 h of isoleucine deprivation [2].
• Reduced expression of (alpha)5(beta)1 integrin prevents spreading-dependent cell proliferation [17].
• Reduced expression of Bak increases cellular resistance to the anticancer agent cisplatin, and we report here that mouse embryo fibroblasts deficient in the SAP kinase jnk1 are highly resistant to apoptosis induced by cisplatin [18].

Physical interactions of Zfp42

• The octamer motif present in the Rex-1 promoter binds Oct-1 and Oct-3 expressed by EC cells and ES cells [1].

Other interactions of Zfp42

• These results provide support for a role of Oct-3 in the transcription of the Rex-1 gene [1].
• Reduced expression of tPA and uPA was seen in EMT6 cells carrying the antisense IGF-IR construct [19].
• Reduced expression of P2Y1 receptors in connexin43-null mice alters calcium signaling and migration of neural progenitor cells [20].
• F9 wild type cells in monolayer culture require both retinoic acid and cyclic AMP analogs to differentiate into PE, whereas the F9 Rex-1(-/-) cells differentiate into PE, as assessed by several molecular markers, including thrombomodulin and laminin B1, in the presence of RA alone [21].
• The F9 Rex-1(-/-) cells do not completely differentiate into VE after RA treatment in aggregate culture; they do not express alpha-fetoprotein, a definitive marker of VE differentiation [21].

Analytical, diagnostic and therapeutic context of Zfp42

• In situ hybridization and northern analyses of RNA from germ-cell-deficient mouse testis and stage-specific germ cell preparations suggest that Rex-1 expression is limited to spermatocytes (germ cells undergoing meiosis) [16].
• Reduced expression of platelet endothelial cell adhesion molecule-1 in bone marrow cells in mice after skeletal unloading [22].
• Rex-1 mRNA expression was determined using both reverse transcription and real-time PCR [23].
• REX1 protein expression was assessed by western analysis and immunohistochemistry, using an affinity-purified, polyclonal antibody to the REX1 protein [23].
• CONCLUSIONS: Reduced expression of either class I or II direct allorecognition pathways is insufficient to prevent the development of chronic rejection, despite a reduction in the levels of TGF-beta expressed in the allograft [24].

References