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‣ Cooperative RNA Polymerase Molecules Behavior on a Stochastic Sequence-Dependent Model for Transcription Elongation

Costa, Pedro Rafael; Acencio, Marcio Luis; Lemke, Ney
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica
Português
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The transcription process is crucial to life and the enzyme RNA polymerase (RNAP) is the major component of the transcription machinery. The development of single-molecule techniques, such as magnetic and optical tweezers, atomic-force microscopy and single-molecule fluorescence, increased our understanding of the transcription process and complements traditional biochemical studies. Based on these studies, theoretical models have been proposed to explain and predict the kinetics of the RNAP during the polymerization, highlighting the results achieved by models based on the thermodynamic stability of the transcription elongation complex. However, experiments showed that if more than one RNAP initiates from the same promoter, the transcription behavior slightly changes and new phenomenona are observed. We proposed and implemented a theoretical model that considers collisions between RNAPs and predicts their cooperative behavior during multi-round transcription generalizing the Bai et al. stochastic sequence-dependent model. In our approach, collisions between elongating enzymes modify their transcription rate values. We performed the simulations in Mathematica® and compared the results of the single and the multiple-molecule transcription with experimental results and other theoretical models. Our multi-round approach can recover several expected behaviors...

‣ Les facteurs à homéodomaine Pitx et Irx au cours du développement des membres postérieurs

Lavertu Jolin, Marisol
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
Português
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Les facteurs de transcription Pitx ont été impliqués dans la croissance et la détermination de l’identité des membres postérieurs. D’abord, l’inactivation de Pitx1 chez la souris résulte en la transformation partielle des membres postérieurs en membres antérieurs. Ensuite, la double mutation de Pitx1 et de Pitx2 a montré l’activité redondante de ces facteurs pour la croissance des membres postérieurs. Ainsi, les souris mutantes Pitx1-/-;Pitx2néo/néo montrent une perte des éléments squelettiques proximaux et antérieurs. Des travaux récents ont impliqué les gènes de la famille des Iroquois dans le développement des membres. Tout particulièrement, les souris Irx3-/-;Irx5-/- montrent la perte des éléments squelettiques proximaux et antérieurs, exclusivement au niveau des membres postérieurs. Cette phénocopie entre les souris mutantes pour Pitx1/2 et Irx3/5 nous a amenés à poser trois hypothèses : (1) les Pitx sont responsables de l’expression de Irx dans les bourgeons postérieurs ; (2) à l’inverse, les Irx dirigent l’expression des Pitx ; (3) les Pitx et les Irx participent ensemble au programme génétique de croissance des bourgeons postérieurs. Nous avons pu conclure que les Pitx et les Irx font partie de cascades de régulation indépendantes l’une de l’autre et qu’ils sont capables d’interaction transcriptionnelle autant sur un promoteur générique que sur des régions conservées du locus de Tbx4. Enfin...

‣ Alternative strategies for deciphering the genetic architecture of childhood Pre-B acute lymphoblastic leukemia

Healy, Jasmine
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
Português
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37.112158%
La leucémie lymphoblastique aigüe (LLA) est une maladie génétique complexe. Malgré que cette maladie hématologique soit le cancer pédiatrique le plus fréquent, ses causes demeurent inconnues. Des études antérieures ont démontrées que le risque à la LLA chez l’enfant pourrait être influencé par des gènes agissant dans le métabolisme des xénobiotiques, dans le maintient de l’intégrité génomique et dans la réponse au stress oxydatif, ainsi que par des facteurs environnementaux. Au cours de mes études doctorales, j’ai tenté de disséquer davantage les bases génétiques de la LLA de l’enfant en postulant que la susceptibilité à cette maladie serait modulée, au moins en partie, par des variants génétiques agissant dans deux voies biologiques fondamentales : le point de contrôle G1/S du cycle cellulaire et la réparation des cassures double-brin de l’ADN. En utilisant une approche unique reposant sur l’analyse d’une cohorte cas-contrôles jumelée à une cohorte de trios enfants-parents, j’ai effectué une étude d’association de type gènes/voies biologiques candidats. Ainsi, j’ai évaluer le rôle de variants provenant de la séquence promotrice de 12 gènes du cycle cellulaire et de 7 gènes de la voie de réparation de l’ADN...

‣ The Role of the Transcription Factor Ets1 in Melanocyte Development

Saldana Tavares, Amy
Fonte: FIU Digital Commons Publicador: FIU Digital Commons
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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Melanocytes, pigment-producing cells, derive from the neural crest (NC), a population of pluripotent cells that arise from the dorsal aspect of the neural tube during embryogenesis. Many genes required for melanocyte development were identified using mouse pigmentation mutants. The deletion of the transcription factor Ets1 in mice results in hypopigmentation; nevertheless, the function of Ets1 in melanocyte development is unknown. The goal of the present study was to establish the temporal requirement and role of Ets1 in murine melanocyte development. In the mouse, Ets1 is widely expressed in developing organs and tissues, including the NC. In the chick cranial NC, Ets1 is required for the expression of Sox10, a transcription factor critical for the development of melanocytes, enteric ganglia, and other NC derivatives. Using a combination of immunofluorescence and cell survival assays Ets1 was found to be required between embryonic days 10 and 11, when it regulates NC cell and melanocyte precursor (melanoblast) survival. Given the requirement of Ets1 for Sox10 expression in the chick cranial NC, a potential interaction between these genes was investigated. Using genetic crosses, a synergistic genetic interaction between Ets1 and Sox10 in melanocyte development was found. Since Sox10 is essential for enteric ganglia formation...

‣ Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor

Doyle, K.; Russell, D.; Sriraman, V.; Richards, J.
Fonte: Endocrine Soc Publicador: Endocrine Soc
Tipo: Artigo de Revista Científica
Publicado em //2004 Português
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ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs) is a multifunctional protease that is expressed in periovulatory follicles. Herein we show that induction of ADAMTS-1 message in vivo and transcription of the ADAMTS-1 promoter in cultured granulosa cells are dependent on separable but coordinate actions of LH and the progesterone receptor (PR). To analyze the molecular mechanisms by which LH and PR regulate this gene, truncations and site-specific mutants of ADAMTS-1 promoter-luciferase reporter constructs (ADAMTS-1-Luc) were generated and transfected into rat granulosa cell cultures. Three regions of the promoter were found to be important for basal activity, two of which were guanine cytosine-rich binding sites for specificity proteins Sp1/Sp3 and the third bound a nuclear factor 1-like factor. Despite the absence of a consensus PR DNA response element in the proximal ADAMTS-1 promoter, cotransfection of a PRA (or PRB) expression vector stimulated ADAMTS-1 promoter activity, a response that was reduced by the PR antagonist ZK98299. Forskolin plus phorbol myristate acetate also increased promoter activity and, when added to cells cotransfected with PRA, ADAMTS-1 promoter activity increased further. Activation of the ADAMTS-1 promoter by PRA involves functional CAAT enhancer binding protein beta...

‣ De novo reverse transcription of HTLV-1 following cell-to-cell transmission of infection

Benovic, S.; Kok, T.; Stephenson, A.; McInnes, J.; Burrell, C.; Li, P.
Fonte: ACADEMIC PRESS INC Publicador: ACADEMIC PRESS INC
Tipo: Artigo de Revista Científica
Publicado em //1998 Português
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Analogous to transmission of human T-cell leukemia virus type 1 (HTLV-1) in vivo, an in vitro cell-to-cell infection model was established by coculturing MT-2 cells as virus donors and HUT78 cells as recipients. At a donor:recipient ratio of 1:2, cell fusion occurred and a new round of HTLV-1 genome replication was initiated in the cocultured cells. Newly synthesized unintegrated viral DNA was detected by Southern blot within 4-8 h and then increased between 8 and 48 h following cell mixing. The most dominant species of unintegrated viral DNA was 3.7 kb in size which hybridized to a full-length HTLV-1 DNA probe but not to a Kpnl viral DNA fragment that is absent from a defective proviral genome that has been previously identified in MT-2 cells. Northern blot analysis showed large amounts of viral RNA in the virus donor cells and in the cocultured cells, with a 3.4-kb species being the most abundant. This 3.4-kb RNA gave a pattern identical to that of the 3.7-kb unintegrated viral DNA in hybridization studies using the two probes. It seems likely that the unspliced RNA transcript from the defective proviral genome in MT-2 cells was effectively reverse transcribed upon initiation of cell-to-cell viral transmission to susceptible HUT78 cells. Despite active de novo reverse transcription...

‣ Molecular evidence for transcription of genes on a B chromosome in Crepis capillaris

Leach, C.; Houben, A.; Field, B.; Pistrick, K.; Demidov, D.; Timmis, J.
Fonte: Genetics Publicador: Genetics
Tipo: Artigo de Revista Científica
Publicado em //2005 Português
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Dispensable, supernumerary (B) chromosomes are found in diverse eukaryotic species. The origin and genetic consequences of B chromosomes have been the subjects of speculation for more than a century. Until now, there has been no molecular evidence that B chromosome DNA is transcribed and there is no unequivocal evidence as to their origin. B chromosomes are considered to be genetically inert although they appear to cause a variety of phenotypic effects. We report that members of one of two ribosomal RNA gene families that are confined to the B chromosomes of a plant, Crepis capillaris, are transcribed—thus providing the first molecular evidence of gene activity on B chromosomes. Sequence analysis of part of the A and B chromosome rRNA genes, together with comparisons with related species, indicates that the B chromosome rRNA genes originate from the A chromosome.; Carolyn R. Leach, Andreas Houben, Bruce Field, Klaus Pistrick, Dmitri Demidov and Jeremy N. Timmis

‣ CBFA2T3-ZNF652 corepressor complex regulates transcription of the E-box gene HEB

Kumar, R.; Cheney, K.; McKirdy, R.; Neilsen, P.; Schulz, R.; Lee, J.; Cohen, J.; Booker, G.; Callen, D.
Fonte: Amer Soc Biochemistry Molecular Biology Inc Publicador: Amer Soc Biochemistry Molecular Biology Inc
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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Transcriptional repression plays a critical role in development and homeostasis. The ETO family represents a group of highly conserved and ubiquitously expressed transcriptional regulatory proteins that are components of a diverse range of multiprotein repressor complexes. ETO proteins function as transcriptional repressors by interacting with a number of transcription factors that bind to their cognate consensus DNA binding sequences within the promoters of target genes. We previously reported that the classical C2H2 zinc finger DNA-binding protein, ZNF652, specifically and functionally interacts with the ETO protein CBFA2T3 and has a role in the suppression of breast oncogenesis. Here we report the identification and validation of the ZNF652 consensus DNA binding sequence. Our results show that the E-box gene HEB is a direct target of CBFA2T3-ZNF652-mediated transcriptional repression. The CBFA2T3-ZNF652 complex regulates HEB expression by binding to a single ZNF652 response element located within the promoter sequence of HEB. This study also shows that the NHR3 and NHR4 domains of CBFA2T3 interact with a conserved proline-rich region located within the C terminus of ZNF652. Our results, together with previous reports, indicate that HEB has a complex relationship with CBFA2T3; CBFA2T3 interacts with ZNF652 to repress HEB expression...

‣ The generation of promoter-mediated transcriptional noise in bacteria

Mitarai, N.; Dodd, I.; Crooks, M.; Sneppen, K.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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Noise in the expression of a gene produces fluctuations in the concentration of the gene product. These fluctuations can interfere with optimal function or can be exploited to generate beneficial diversity between cells; gene expression noise is therefore expected to be subject to evolutionary pressure. Shifts between modes of high and low rates of transcription initiation at a promoter appear to contribute to this noise both in eukaryotes and prokaryotes. However, models invoked for eukaryotic promoter noise such as stable activation scaffolds or persistent nucleosome alterations seem unlikely to apply to prokaryotic promoters. We consider the relative importance of the steps required for transcription initiation. The 3-step transcription initiation model of McClure is extended into a mathematical model that can be used to predict consequences of additional promoter properties. We show in principle that the transcriptional bursting observed at an E. coli promoter by Golding et al. (2005) can be explained by stimulation of initiation by the negative supercoiling behind a transcribing RNA polymerase (RNAP) or by the formation of moribund or dead-end RNAP-promoter complexes. Both mechanisms are tunable by the alteration of promoter kinetics and therefore allow the optimization of promoter mediated noise.; Namiko Mitarai...

‣ dLKR/SDH regulates hormone-mediated histone arginine methylation and transcription of cell death genes

Cakouros, D.; Mills, K.; Denton, D.; Paterson, A.; Daish, T.; Kumar, S.
Fonte: Rockefeller Univ Press Publicador: Rockefeller Univ Press
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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The sequential modifications of histones form the basis of the histone code that translates into either gene activation or repression. Nuclear receptors recruit a cohort of histone-modifying enzymes in response to ligand binding and regulate proliferation, differentiation, and cell death. In Drosophila melanogaster, the steroid hormone ecdysone binds its heterodimeric receptor ecdysone receptor/ultraspiracle to spatiotemporally regulate the transcription of several genes. In this study, we identify a novel cofactor, Drosophila lysine ketoglutarate reductase (dLKR)/saccharopine dehydrogenase (SDH), that is involved in ecdysone-mediated transcription. dLKR/SDH binds histones H3 and H4 and suppresses ecdysone-mediated transcription of cell death genes by inhibiting histone H3R17me2 mediated by the Drosophila arginine methyl transferase CARMER. Our data suggest that the dynamic recruitment of dLKR/SDH to ecdysone-regulated gene promoters controls the timing of hormone-induced gene expression. In the absence of dLKR/SDH, histone methylation occurs prematurely, resulting in enhanced gene activation. Consistent with these observations, the loss of dLKR/SDH in Drosophila enhances hormone-regulated gene expression, affecting the developmental timing of gene activation.; Dimitrios Cakouros...

‣ Reverse transcription with random pentadecamer primers improves the detection limit of a quantitative PCR assay for BCR-ABL transcripts in chronic myeloid leukemia: Implications for defining sensitivity in minimal residual disease

Ross, D.; Watkins, D.; Hughes, T.; Branford, S.
Fonte: Amer Assoc Clinical Chemistry Publicador: Amer Assoc Clinical Chemistry
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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Background: Real-time quantitative reverse transcription PCR (RQ-PCR) assay for BCR-ABL is used to monitor treatment response in chronic myeloid leukemia (CML). BCR-ABL transcript levels decline over several years of imatinib treatment, and increasing numbers of patients have BCR-ABL transcripts at or below the limit of detection. More sensitive PCR methods are required to assess whether these patients have a long-term continuing decline in residual disease. Methods: We used random pentadecamer (R15) primers for reverse transcription in RQ-PCR and compared the results with our established method that uses random hexamers. An increase in assay sensitivity would be detected as an increase in the number of BCR-ABL transcripts. Results: BCR-ABL transcripts increased by 86% with R15 primers. We used R15 primers to retest 19 samples from selected CML patients who had no BCR-ABL transcripts recently detectable with hexamer primers and detected BCR-ABL transcripts in 68% of the samples. Use of R15 primers showed variable increases in the transcripts for control genes BCR (breakpoint cluster region), ABL1 (c-abl oncogene 1, receptor tyrosine kinase), and GUSB (glucuronidase, beta), depending on the gene examined. The reported BCR-ABL/control gene ratio was affected...

‣ The Transcription factor encyclopedia

Yusuf, D.; Olechnowicz, S.; Peet, D.
Fonte: BioMed Central Ltd. Publicador: BioMed Central Ltd.
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
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Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field.; Dimas Yusuf... Sam W.Z.Olechnowicz... Daniel J. Peet... et al.

‣ Control of gene expression in the temperate coliphage 186. X. The cl repressor directly represses transcription of the late control gene B

Dibbens, J.A.; Gregory, S.L.; Egan, J.B.
Fonte: Wiley Publicador: Wiley
Tipo: Artigo de Revista Científica
Publicado em //1992 Português
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We have found that the repressor of 186 lytic transcription, CI, represses transcription of the late control gene B, with no involvement of the B protein Itself. In clone studies we showed that CI repressed transcription from the B promoter and that temperature inactivation of CIts led to B derepression. We conclude that CI repressor directly represses transcription of the Bgene and, with prophage induction, it is probable that the inactivation of the CI repressor not only derepresses early lytic transcription, but also derepresses B gene transcription, leading to the activation of transcription from the late promoters.; Justin A. Dibbens, Stephen L. Gregory and J. Barry Egan

‣ A novel role for the Pol I transcription factor UBTF in maintaining genome stability through the regulation of highly transcribed Pol II genes

Sanij, E.; Diesch, J.; Lesmana, A.; Poortinga, G.; Lidgerwood, G.; Hein, N.; Cameron, D.P.; Ellul, J.; Goodall, G.J.; Wong, L.H.; Dhillon, A.S.; Hamdane, N.; Rothblum, L.I.; Pearson, R.B.; Haviv, I.; Moss, T.; Hannan, R.D.
Fonte: CSH Press Publicador: CSH Press
Tipo: Artigo de Revista Científica
Publicado em //2015 Português
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Mechanisms to coordinate programs of highly transcribed genes required for cellular homeostasis and growth are unclear. Upstream binding transcription factor 1 (UBTF, also called UBF) is thought to function exclusively in RNA polymerase I (Pol I)-specific transcription of the ribosomal genes. Here we report that, the two isoforms of UBTF (UBTF1/2) are also enriched at highly expressed Pol II-transcribed genes throughout the mouse genome. Further analysis of UBTF1/2 DNA binding in immortalised human epithelial cells and their isogenically matched transformed counterparts reveals an additional repertoire of UBTF1/2-bound genes involved in the regulation of cell cycle checkpoints and DNA damage response. As proof of a functional role for UBTF1/2 in regulating Pol II transcription, we demonstrate that UBTF1/2 is required for recruiting Pol II to the highly transcribed histone gene clusters and for their optimal expression. Intriguingly, lack of UBTF1/2 does not affect chromatin marks or nucleosome density at histone genes. Instead it results in increased accessibility of the histone promoters and transcribed regions to micrococcal nuclease, implicating UBTF1/2 in mediating DNA accessibility. Unexpectedly, UBTF2, which does not function in Pol I transcription...

‣ A NF-kappa B/Sp1 region is essential for chromatin remodeling and correct transcription of a human granulocyte-macrophage colony-stimulating factor transgene

Cakouros, D.; Cockerill, P.N.; Bert, A.G.; Mital, R.; Roberts, D.C.; Shannon, M.F.
Fonte: American Association of Immunologists Publicador: American Association of Immunologists
Tipo: Artigo de Revista Científica
Publicado em //2001 Português
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The GM-CSF gene is expressed following activation of T cells. The proximal promoter and an upstream enhancer have previously been characterized using transfection and reporter assays in T cell lines in culture. A 10.5-kb transgene containing the entire human GM-CSF gene has also been shown to display inducible, position-independent, copy number-dependent transcription in mouse splenocytes. To determine the role of individual promoter elements in transgene function, mutations were introduced into the proximal promoter and activity assessed following the generation of transgenic mice. Of four mutations introduced into the transgene promoter, only one, in an NF-kappaB/Sp1 region, led to decreased induction of the transgene in splenocytes or bone marrow-derived macrophages. This mutation also affected the activity of reporter gene constructs stably transfected into T cell lines in culture, but not when transiently transfected into the same cell lines. The mutation alters the NF-kappaB family members that bind to the NF-kappaB site as well as reducing the binding of Sp1 to an adjacent element. A DNase I hypersensitive site that is normally generated at the promoter following T cell activation on the wild-type transgene does not appear in the mutant transgene. These results suggest that the NF-kappaB/Sp1 region plays a critical role in chromatin remodeling and transcription on the GM-CSF promoter in primary T cells.; Dimitrios Cakouros...

‣ DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription

Zamudio, N.; Scott, H.; Wolski, K.; Lo, C.Y.; Law, C.; Leong, D.; Kinkel, S.; Chong, S.; Jolley, D.; Smyth, G.; De Kretser, D.; Whitelaw, E.; O'Bryan, M.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
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Previous studies on the epigenetic regulator DNA methyltransferase 3-Like (DNMT3L), have demonstrated it is an essential regulator of paternal imprinting and early male meiosis. Dnmt3L is also a paternal effect gene, i.e., wild type offspring of heterozygous mutant sires display abnormal phenotypes suggesting the inheritance of aberrant epigenetic marks on the paternal chromosomes. In order to reveal the mechanisms underlying these paternal effects, we have assessed X chromosome meiotic compaction, XY chromosome aneuploidy rates and global transcription in meiotic and haploid germ cells from male mice heterozygous for Dnmt3L. XY bodies from Dnmt3L heterozygous males were significantly longer than those from wild types, and were associated with a three-fold increase in XY bearing sperm. Loss of a Dnmt3L allele resulted in deregulated expression of a large number of both X-linked and autosomal genes within meiotic cells, but more prominently in haploid germ cells. Data demonstrate that similar to embryonic stem cells, DNMT3L is involved in an autoregulatory loop in germ cells wherein the loss of a Dnmt3L allele resulted in increased transcription from the remaining wild type allele. In contrast, however, within round spermatids, this auto-regulatory loop incorporated the alternative noncoding alternative transcripts. Consistent with the mRNA data...

‣ Integration of transcript and genetic maps of chromosome 16 at near-1-Mb resolution: demonstration of a 'hot-spot' for recombination at 16p12

Callen, D.; Lane, S.; Kozman, H.; Kremmidiotis, G.; Whitmore, S.; Lowenstein, M.; Doggett, N.; Kenmochi, N.; Page, D.; Maglott, D.; Nierman, W.; Murakawa, K.; Sikela, J.; Houlgatte, R.; Auffray, C.; Sutherland, G.
Fonte: Academic Press Publicador: Academic Press
Tipo: Artigo de Revista Científica
Publicado em //1995 Português
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A single mapping resource, a mouse/human somatic cell panel with average distance between breakpoints of 1.2 Mb and a potential resolution of 1 Mb, has been utilized to integrate the genetic map and a transcript map of human chromosome 16. This map includes 141 genetic markers and 200 genes and transcripts. The localization of four genes (CHEL3, TK2, TRG1, and MMP9) reported to map to chromosome 16 could not be confirmed, and for three of these localizations to other human chromosomes are reported. A correlation between genetic and physical distance over a region estimated to be 23 Mb on the short arm of chromosome 16 identified an interval demonstrating a greatly increased rate of recombination where, in females, 1 cM is equivalent to a physical distance of 100 kb.

‣ Control of gene expression in the temperate coliphage 186 : VIII. Control of lysis and lysogeny by a transcriptional switch involving face-to-face promoters

Dodd, I.B.; Kalionis, B.; Egan, J.B.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //1990 Português
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The lysogenic and early lytic operons of the temperate coliphage 186 are transcribed divergently. Primer extension mapping of the 5' ends of these in vivo transcripts showed that the rightward lytic promoter, pR, and the leftward lysogenic promoter, pL, are arranged face-to-face, with their transcripts overlapping by 60 bases. We examined the control of transcription from pR and pL using galK as a reporter gene. The product of the lysogenic cI gene strongly repressed pR transcription while allowing pL transcription. The product of the lytic apl gene (formerly CP75) strongly repressed pL transcription while allowing pR transcription. Thus, the cI-pR-pL-apl region functioned as a transcriptional switch, determining whether transcription was lytic or lysogenic. Also, the cI gene product was able to stimulate pL, possibly by alleviating an inhibition of pL transcription caused by convergent transcription from pR. Other consequences of the face-to-face promoter arrangement are discussed.; Ian B. Dodd, Bill Kalionis and J. Barry Egan

‣ Global Analysis of Genetic, Epigenetic and Transcriptional Polymorphisms in Arabidopsis thaliana Using Whole Genome Tiling Arrays

Zhang, Xu; Shiu, Shinhan; Cal, Andrew; Borevitz, Justin O.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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46.617515%
Whole genome tiling arrays provide a high resolution platform for profiling of genetic, epigenetic, and gene expression polymorphisms. In this study we surveyed natural genomic variation in cytosine methylation among Arabidopsis thaliana wild accessions Columbia (Col) and Vancouver (Van) by comparing hybridization intensity difference between genomic DNA digested with either methylation-sensitive (HpaII) or -insensitive (MspI) restriction enzyme. Single Feature Polymorphisms (SFPs) were assayed on a full set of 1,683,620 unique features of Arabidopsis Tiling Array 1.0F (Affymetrix), while constitutive and polymorphic CG methylation were assayed on a subset of 54,519 features, which contain a 5'CCGG3' restriction site. 138,552 SFPs (1% FDR) were identified across enzyme treatments, which preferentially accumulated in pericentromeric regions. Our study also demonstrates that at least 8% of all analyzed CCGG sites were constitutively methylated across the two strains, while about 10% of all analyzed CCGG sites were differentially methylated between the two strains. Within euchromatin arms, both constitutive and polymorphic CG methylation accumulated in central regions of genes but under-represented toward the 5' and 3' ends of the coding sequences. Nevertheless...

‣ Hypothesis: A biological role for germline transcription in the mechanism of V(D)J recombination - implications for initiation of allelic exclusion

Franklin, Andrew
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Português
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The sequences that encode the antigen-binding sites of IgH and IgL chains - variable (V), diversity (D, H chain loci only) and joining (J) sequences - are configured as separate DNA segments at the germline level. Expression of an Ig molecule requires V(D)J assembly. Productive V(D)J recombination is monoallelic. How rearrangement is initiated differentially at maternal and paternal alleles is unclear. The products of recombination activating gene (RAG)1 and RAG2 mediate rearrangement by cleaving the DNA between an unrearranged gene segment and adjacent recombination signal sequences (RSS). It is proposed that supercoiling generated during germline transcription at Ig loci (which occurs concomitantly with rearrangement) is required at RSS for RAG1/2 recognition. Rearrangement might hence initiate sequentially at maternal and paternal alleles where deregulated germline transcription causes RAG1/2 recognition of RSS to become stochastic.