Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cDNA sequence of Stra7, a retinoic acid (RA)-inducible gene in P19 embryonal carcinoma (EC) cells, was determined. The deduced Stra7 protein contains a homeodomain highly similar to that of the previously described chicken CHox7 gene product, and is highly conserved during evolution, from hemichordates to vertebrates. The mouse Stra7 cDNA corresponds to the full-length form of the 77 bp homeodomain-encoding cDNA fragment which was previously cloned and termed MMoxA or Gbx-2. Reverse-transcriptase-PCR analysis revealed the presence of Stra7/Gbx-2 transcripts in the adult brain, spleen, and female genital tract, whereas no expression could be observed in heart, liver, lung, kidney, or testes. In situ hybridization analysis showed a restricted expression pattern of Stra7/Gbx-2 in the three primitive germ layers during gastrulation. Restricted expression was also detected in the pharyngeal arches. Subsequently, there were specific expression domains in the developing central nervous system, at the midbrain/hindbrain boundary and later in the cerebellum anlage, in certain rhombomeres, in dorsal regions of the spinal cord, and in the developing dorsal thalamus and corpus striatum.
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PMID:Sequence and expression pattern of the Stra7 (Gbx-2) homeobox-containing gene induced by retinoic acid in P19 embryonal carcinoma cells. 860 Oct 31

Exposure of aggregated murine P19 embryonal carcinoma cells to dimethylsulfoxide (DMSO) induces mesoderm and both embryonic cardiac and skeletal muscle differentiation, while retinoic acid (RA) is an inducer of neuroectodermal differentiation. P19 cells constitutively express the retinoic acid receptor alpha (RAR alpha) and RAR gamma mRNAs while RAR beta expression is induced by RA through a consensus RA-response element in the RAR beta promoter. In the present study we show that the RAR beta transcript is strongly expressed in both P19 cells and in a RA-nonresponsive derivative of P19 cells, called RAC65, during DMSO-induced mesoderm and muscle differentiation. Reverse transcriptase-polymerase chain reaction analysis indicated that RAR beta 2 is the predominant isoform expressed in DMSO-differentiated cells, providing the first evidence for RA-independent regulation of RAR beta 2 transcript levels. Immunoblot analysis showed a 3-fold increase in the RAR beta protein expression over basal levels in differentiated cells, and immunohistochemistry indicated that all cells in the culture including muscle reacted positively for the RAR beta protein. RAR beta 2 transcript expression was differentiation-dependent and occurred without transactivation of a transfected RARE beta 2 reporter gene. Little transcription of the RAR beta gene was detected in nuclear run-off assays of undifferentiated P19 cells and only a small increase in transcription was observed in nuclei from DMSO-treated cells. RA treatment of P19 cells stably transfected with the RA-responsive element from the RAR beta gene showed that RAR beta 2 mRNA expression during DMSO differentiation was associated with increased sensitivity to RA. Together these data show that RAR beta 2 is expressed spontaneously in an apparently RA-independent manner in differentiating mesoderm and mesoderm derivatives, resulting in increased sensitivity to RA in these cells.
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PMID:Spontaneous retinoic acid receptor beta 2 expression during mesoderm differentiation of P19 murine embryonal carcinoma cells. 1092 6

The murine Nanog gene, a member of the homeobox family of DNA binding transcription factors, has been shown recently to maintain pluripotency of embryonic stem cells. We have used a sequence homology and expression screen to identify and clone the mouse and human Nanog genes and characterized their phylogenetic context and expression patterns. We report here the gene structure and expression patterns of the mouse Nanog gene, the human Nanog and Nanog2 genes, and six processed human Nanog pseudogenes. Mouse Nanog expression is high in undifferentiated embryonic stem cells and is down-regulated during embryonic stem cell differentiation, concomitant with loss of pluripotency. Murine embryonic Nanog expression is detected in the inner cell mass of the blastocyst. After implantation, Nanog is detectable at embryonic day (E) 6 in proximal epiblast in the region of the presumptive primitive streak. Expression extends distally as the streak elongates during gastrulation and remains restricted to epiblast. Nanog RNA is down-regulated in cells ingressing through the streak to form mesoderm and definitive endoderm. Nanog expression also marks the pluripotent germ cells of the nascent gonad at E11.5-E12.5 and is highly expressed in germ cell tumour and teratoma-derived cell lines. Reverse transcriptase-polymerase chain reaction analysis detected mouse Nanog expression at low levels in several adult tissues. The human Nanog genes are expressed in embryonic stem cells and down-regulated in all adult tissues and differentiated cell lines examined. High levels of human Nanog expression were detected by Northern analysis in the undifferentiated N-Tera embryonal carcinoma cell line. The conservation in gene sequence, structure, and expression of mouse and human Nanog and Nanog2 genes may reflect a common role in the maintenance of pluripotency in both species.
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PMID:Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human. 1510 23

Testicular germ cell tumors (TGCTs), comprised of seminomas and non-seminomas, are derived from premalignant and noninvasive intracellular germ cell neoplasias. Among TGCTs, seminomas are believed to resemble a transformed state of primordial germ cells (PGCs) and are known to exhibit a gene expression profile similar to that of embryonic stem (ES) cells, such as transcription factor OCT-4. OCT-4 has recently been recognized as a diagnostic marker for clinical aspects of seminomas. However, the role of the OCT-4 protein in seminomas has not been clarified. To determine a possible role of the OCT-4 protein in seminomas, in this paper, we studied a series of 41 testicular tumor tissues and four cell lines by immunohistochemistry, Western blotting, and reverse-transcriptase polymerase chain reaction (RT-PCR) to examine the expression and distribution of the OCT-4 transcription factor in seminomas. By utilizing immunohistochemical staining and Western blotting, we demonstrated that the OCT-4 transcription factor was aberrantly localized in the cytoplasm and nuclei of cells in the collected seminoma tissues. This observation was further confirmed using immunocytochemical staining of NCCIT (seminoma-embryonal carcinoma) and NT2 (embryonal carcinoma) cells. In addition, the RT-PCR results indicated that Oct-4 mRNA was relatively highly expressed in NCCIT, NT2 cells, and seminoma tissues when compared with human embryonic stem cells. The aberrant expression and distribution of the OCT-4 transcription factor in seminomas may provide some important clues concerning the cell transformation between germ line stem cells (like PGC) and testicular germ cell tumors.
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PMID:Aberrant expression and distribution of the OCT-4 transcription factor in seminomas. 1768 39

Various compounds, including therapeutic drugs, can adversely impact the survival and development of embryos in the uterus. Identification of such development-interfering agents is a challenging task, although multi-angle approaches--including the use of in vitro toxicology studies involving embryonic stem cells--should alleviate some of the current difficulties. In the present study, we utilized the in vitro elongation of embryoid bodies (EBs) derived from mouse embryonal carcinoma stem cell line P19C5 as a model of early embryological events, specifically that of gastrulation and axial patterning. From our study, we identified donepezil, a medication indicated for the management of Alzheimer's disease, as a potential developmental toxicant. The extent of P19C5 EB axial elongation was diminished by donepezil in a dose-dependent manner. Although donepezil is a known inhibitor of acetylcholinesterase, interference of elongation was not mediated through this enzyme. Quantitative reverse-transcriptase PCR revealed that donepezil altered the expression pattern of a specific set of developmental regulator genes involved in patterning along the anterior-posterior body axis. When tested in mouse whole embryo culture, donepezil caused morphological abnormalities including impaired somitogenesis. Donepezil also diminished elongation morphogenesis of EBs generated from human embryonic stem cells. These results suggest that donepezil interferes with axial elongation morphogenesis of early embryos by altering the expression pattern of regulators of axial development.
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PMID:Morphology-based mammalian stem cell tests reveal potential developmental toxicity of donepezil. 2526 81