Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 histone H3 and H4 genes are shown to be expressed in both Arabidopsis plantlets and transitory multicellular suspension. The 5'- and 3'-ends of the H4 mRNAs have been localized on two H4 genes previously sequenced, H4A748 and H4A777. S1-nuclease mapping and reverse-transcriptase-primer-elongation experiments revealed the existence of two start points for transcription, located 31 and 37 nucleotides downstream from the TATA-box. The 3'-end of the mRNA corresponding to H4A748 was localized at 177 nt after the stop codon. The other gene, H4A777, most probably is not expressed. In addition to a long 3'-untranslated region, the H4 mRNA was shown to be polyadenylated in both plantlets and cell-suspension. This observation was extended to the H3 mRNAs of Arabidopsis and of two other dicots, tobacco and sunflower. Previous results on maize H3 and H4 mRNAs suggest that polyadenylation is a common feature for histone mRNAs in higher plants.
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PMID:Polyadenylation of histone H3 and H4 mRNAs in dicotyledonous plants. 290 89

Arsenic compounds, Including arsenic trioxide (As2O3) and arsenic sulfide (As4S4), have recently been shown to be effective in the treatment of acute promyelocytic leukemia (APL). In vitro, As2O3 exerts a dose-dependent dual effect: it triggers apoptosis at relatively high concentrations (0.5 to 2.0 micromol/L) and induces partial differentiation at low concentrations (0.1 to 0.5 micromol/L). The apoptosis-inducing effect is associated with the collapse of mitochondrial transmembrane potentials in a thiol-dependent manner, whereas the retinoic acid signaling is required for APL cell differentiation. As2O3 over a wide range of concentrations (0.1 to 2.0 micromol/L) Induces degradation of PML-RARalpha as well as the wild-type PML and enhances the acetylation of histone, a process important for the transcriptional activation of genes. In vivo, As2O3 induces a high complete remission (CR) rate in patients with both primary and relapsed APL (around 85% to 90%). Side effects, such as skin reaction, gastrointestinal symptoms, electrocardiographic (EKG) changes, neuropathy, and liver dysfunction, are mild to moderate in relapsed patients, and severe hepatic lesions have been found in some primary cases. After CR obtained in relapsed patients, chemotherapy in combination with As2O3 as postremission therapy has yielded better survival than treatment with As2O3 alone. This is in line with the observation that remission induction with As2O3 is not sufficient in most cases to obtain a molecular remission as Judged by reverse-transcriptase polymerase chain reaction for PML-RARalpha fusion transcripts. The in vivo effect of As2O3 seems to be related to the expression of APL-specific PML-RARalpha oncoprotein, and a synergistic effect between As2O3 and ATRA has been shown in the APL mouse model. Besides As2O3, other arsenic compounds such as As4S4 also show a therapeutic effect in APL. Because the toxic effects of arsenic treatment in primary APL need to be investigated further, we propose use of ATRA as a first-line drug for remission induction in primary APL, whereas As2O3 can be incorporated into multidrug postremission therapy or used as rescue for relapsed APL patients.
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PMID:Treatment of acute promyelocytic leukemia with arsenic compounds: in vitro and in vivo studies. 1117 37

The localization of reverse transcriptase-related proteins in polytene chromosomes of dipterans was investigated using previously characterized antibodies to a recombinant polypeptide containing conserved motifs of insect reverse transcriptases. The immunoreactions were carried out with polytene chromosome squashes of eight sciarids, one chironomid and three Drosophila species. Telomeric staining was regularly observed on chromosomes of the sciarid Rhynchosciara americana under normal growth conditions. Five of eight chromosomal tips were labelled except for the heterochromatic ends that are occasionally found associated forming a chromocentre in the salivary gland. Reverse transcriptase-related proteins were detected at chromosomal tips of young larvae and remained bound to the telomeres throughout larval development. As in salivary gland chromosomes, five non-telocentric ends of the chromosomes from Malpighian tubules of R. americana appeared clearly stained with anti-reverse transcriptase. The occurrence of telomeric reverse transcriptase in R. americana correlates with the presence of RNA in addition to an unusual enrichment with homopolymeric dA/dT DNA associated with the telomeric heterochromatin. The antibodies also reacted with a few interstitial sites in chromosomes of four Rhynchosciara species, one band overlapping the histone gene locus of three species in the americana -like group. The results provide evidence for a reverse transcriptase-related protein as a constitutive component in telomeres of R. americana and also in certain interstitial loci of Rhynchosciara species in which RNA was immunologically detected in the form of RNA:DNA hybrids.
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PMID:Reverse transcriptase-related proteins in telomeres and in certain chromosomal loci of Rhynchosciara (Diptera: Sciaridae). 1270 82

In human prostate cancer cells, the availability of the steroid hormone 1,25-dihydroxyvitamin D(3) for antimitotic action is determined through the activity of the two enzymes CYP24 and CYP27B1, viz. 25-hydroxyvitamin D-24-hydroxylase and 25-hydroxyvitamin D-1alpha-hydroxylase. High performance liquid chromatography (HPLC) analysis of [(3)H]25(OH)D(3) metabolism in human prostate cancer DU-145 cells revealed that genistein and other isoflavonoids, such as dihydrogenistein and daidzein, as well as the antiestrogenic compound ICI 182,780, inhibited Vitamin D-metabolizing enzyme activities. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that only in case of genistein this was due to transcriptional inhibition of CYP24 and CYP27B1 gene expressions. In case of CYP27B1, reduction of gene activity involves histone deacetylation because genistein was inactive in the presence of the histone deactylase inhibitor trichostatin A. In contrast, under the same condition, CYP24 gene activity was largely suppressed. In summary, our results suggest that a combined effect of genistein and trichostatin A could increase the responsiveness of human prostate cancer cells to the antiproliferative action of 1,25-dihydroxyvitamin D(3).
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PMID:Genistein inhibits vitamin D hydroxylases CYP24 and CYP27B1 expression in prostate cells. 1273 87

HD2 (histone deacetylase) proteins are plant-specific histone deacetylases (HDACs). The Arabidopsis genome contains four HD2 genes, namely HD2A, HD2B, HD2C, and HD2D. We have previously demonstrated that HD2A, HD2B, and HD2C can repress transcription directly by targeting to promoters in planta. Here, we show that the N-terminal conserved motif (EFWG) and histidine 25 (H25), a potential catalytic residue, were important for the gene repression activity of HD2A. In situ hybridization indicated that HD2A, HD2B, and HD2C were expressed in ovules, embryos, shoot apical meristems, and primary leaves. Furthermore, all three genes were strongly induced during the process of somatic embryogenesis. HD2D mRNA was only detected in the stems and flowers with young siliques and may have adopted different functions. Using green fluorescent protein (GFP) fusions, we demonstrated that HD2A, HD2B, and HD2C accumulated in the nuclei of Arabidopsis cells. Overexpression of 35S::GFP-HD2A in transgenic Arabidopsis plants generated pleiotropic developmental abnormalities, including abnormal leaves, delayed flowering, and aborted seed development. The data showed that normal pattern of HD2 expression was essential for normal plant development and that HD2A, HD2B, and HD2C may be needed for embryogenesis and embryo development. Reverse transcriptase (RT)-PCR analysis revealed that a number of genes involved in seed development and maturation were repressed in the 35S::GFP-HD2A plants, supporting a role of HD2A in the regulation of gene expression during seed development.
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PMID:Expression and function of HD2-type histone deacetylases in Arabidopsis development. 1514 74

Retinoids have shown significant activities in cancer prevention and therapy. Many of their effects are mediated by nuclear retinoid receptors including retinoic acid receptors (RARs alpha, beta and gamma) and retinoid X receptors (RXRs alpha, beta and gamma). Human retinoic acid receptor beta (RARbeta) has three different isoforms: beta1, beta2 and beta4. The tumor suppressive characteristics of RARbeta2, its silencing by promoter hypermethylation, and its reexpression following demethylation have been reported. In contrast, RARbeta1, an embryonic isoform with restricted expression in adult tissues has been linked to carcinogenesis. However, factors regulating RARbeta1 expression have not yet been clarified. During studies on the head and neck squamous cell carcinoma cells, we found that the expression of RARbeta increased in cells grown to high density. Real-time reverse-transcriptase polymerase chain reaction revealed that the isoform increased in these cells was RARbeta1. Epigenetic modifications of this isoform were tested using combined bisulfite restriction analysis and chromatin immunoprecipitation assays. The UMSCC38 cell line showed significant RARbeta1 expression (p < 0.001), which was dependent on cell density and culture duration. The increased expression of RARbeta1 was not due to demethylation of its promoter. However, higher cell densities were associated with increased acetylation of histone 3 at lysine 9 in RARbeta1 but not in RARbeta2. These findings reveal that the expression of RARbeta1 is regulated by cell density through changes in histone acetylation.
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PMID:Regulation of RARbeta1 expression in head and neck cancer cells by cell density-dependent chromatin remodeling. 1546 35

In the context of yet unclarified issues of RNA interference (RNAi), it is discussed that RNAi-induced histone modification may not only have the purpose of inactivating native genes by blocking their transcription in the sense direction but may also simultaneously trigger transcription of the corresponding antisense strand to form double-stranded RNA for posttranscriptional gene-silencing in cells lacking RNA replicase activities. Invading foreign genetic traits may be posttranscriptionally silenced through complementary transcripts from specific, highly variable genomic regions, which are able to finally match any given sequence by the appropriate recombination and processing of their transcripts. The information to fight these traits may additionally become anchored in the genome, to provide at least a temporary "immunity" and may be inherited at least for a few generations. It is further proposed that: (1) RNA viruses evolved from constituents of the RNAi machinery through the capture of functions essential for their maintenance and replication and (2) viruses and RNAi are mutually interacting components of a universal and predominant genetic steering system that is involved in the modulation of gene expression on the cellular level and simultaneously constitutes a driving force for evolution, particularly in imperfect organisms. Such a model would deliver explanations for yet unresolved issues of RNAi, the clarification of which will have a significant impact on its future medical and biotechnological application.
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PMID:About the nature of RNA interference. 1570 9

Double-stranded RNA has been shown to induce gene silencing in diverse eukaryotes and by a variety of pathways. We have examined the taxonomic distribution and the phylogenetic relationship of key components of the RNA interference (RNAi) machinery in members of five eukaryotic supergroups. On the basis of the parsimony principle, our analyses suggest that a relatively complex RNAi machinery was already present in the last common ancestor of eukaryotes and consisted, at a minimum, of one Argonaute-like polypeptide, one Piwi-like protein, one Dicer, and one RNA-dependent RNA polymerase. As proposed before, the ancestral (but non-essential) role of these components may have been in defense responses against genomic parasites such as transposable elements and viruses. From a mechanistic perspective, the RNAi machinery in the eukaryotic ancestor may have been capable of both small-RNA-guided transcript degradation as well as transcriptional repression, most likely through histone modifications. Both roles appear to be widespread among living eukaryotes and this diversification of function could account for the evolutionary conservation of duplicated Argonaute-Piwi proteins. In contrast, additional RNAi-mediated pathways such as RNA-directed DNA methylation, programmed genome rearrangements, meiotic silencing by unpaired DNA, and miRNA-mediated gene regulation may have evolved independently in specific lineages.
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PMID:On the origin and functions of RNA-mediated silencing: from protists to man. 1669 18

Small interfering RNA (siRNA) guides dimethylation of histone H3 lysine-9 (H3K9me2) via the Argonaute and RNA-dependent RNA polymerase complexes, as well as base-pairing with either RNA or DNA. We show that Argonaute requires the conserved aspartate-aspartate-histidine motif for heterochromatic silencing and for ribonuclease H-like cleavage (slicing) of target messages complementary to siRNA. In the fission yeast Schizosaccharomyces pombe, heterochromatic repeats are transcribed by polymerase II. We show that H3K9me2 spreads into silent reporter genes when they are embedded within these transcripts and that spreading requires read-through transcription, as well as slicing by Argonaute. Thus, siRNA guides histone modification by basepairing interactions with RNA.
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PMID:Argonaute slicing is required for heterochromatic silencing and spreading. 1693 64

Paramutation and transposon silencing are two epigenetic phenomena that have intrigued and puzzled geneticists for decades. Each involves heritable changes in gene activity without changes in DNA sequence. Here we report the cloning of a gene whose activity is required for the maintenance of both silenced transposons and paramutated color genes in maize. We show that this gene, Mop1 (Mediator of paramutation1) codes for a putative RNA-dependent RNA polymerase, whose activity is required for the production of small RNAs that correspond to the MuDR transposon sequence. We also demonstrate that although Mop1 is required to maintain MuDR methylation and silencing, it is not required for the initiation of heritable silencing. In contrast, we present evidence that a reduction in the transcript level of a maize homolog of the nucleosome assembly protein 1 histone chaperone can reduce the heritability of MuDR silencing. Together, these data suggest that the establishment and maintenance of MuDR silencing have distinct requirements.
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PMID:Initiation, establishment, and maintenance of heritable MuDR transposon silencing in maize are mediated by distinct factors. 2007 77


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