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| 2. |
- Balagopal, Vidya, et al.
(författare)
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Ways and means of eukaryotic mRNA decay
- 2012
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Ingår i: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. - New York : Elsevier. - 1874-9399. ; 1819:6, s. 593-603
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Forskningsöversikt (refereegranskat)abstract
- Messenger RNA degradation is an important point of control for gene expression. Genome-wide studies on mRNA stability have demonstrated its importance in adaptation and stress response. Most of the key players in mRNA decay appear to have been identified. The study of these proteins brings insight into the mechanism of general and specific targeting of transcripts for degradation. Recruitment and assembly of mRNP complexes enhance and bring specificity to mRNA decay. mRNP complexes can form larger structures that have been found to be ubiquitous in nature. Discovery of P-Bodies, an archetype of this sort of aggregates, has generated interest in the question of where mRNA degrades. This is currently an open question under extensive investigation. This review will discuss in detail the recent developments in the regulation of mRNA decay focusing on yeast as a model system.
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| 4. |
- Henriksson, Richard, et al.
(författare)
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PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain
- 2014
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier. - 0006-3002 .- 1878-2434. ; 1839:11, s. 1226-1232
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Tidskriftsartikel (refereegranskat)abstract
- The dynorphin κ-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders.
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| 5. |
- Kruczyk, Marcin, et al.
(författare)
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Integration of genome-wide of Stat3 binding and epigenetic modification mapping with transcriptome reveals novel Stat3 target genes in glioma cells
- 2014
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434. ; 1839:11, s. 1341-1350
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many human tumors, including gliomas, and regulates the expression of genes implicated in proliferation, survival, apoptosis, angiogenesis and immune regulation. Only a small fraction of those genes has been proven to be direct STAT3 targets. In gliomas, STAT3 can play tumor suppressive or oncogenic roles depending on the tumor genetic background with target genes being largely unknown.RESULTS: We used chromatin immunoprecipitation, promoter microarrays and deep sequencing to assess the genome-wide occupancy of phospho (p)-Stat3 and epigenetic modifications of H3K4me3 and H3ac in C6 glioma cells. This combined assessment identified a list of 1200 genes whose promoters have both Stat3 binding sites and epigenetic marks characteristic for actively transcribed genes. The Stat3 and histone markings data were also intersected with a set of microarray data from C6 glioma cells after inhibition of Jak2/Stat3 signaling. Subsequently, we found 284 genes characterized by p-Stat3 occupancy, activating histone marks and transcriptional changes. Novel genes were screened for their potential involvement in oncogenesis, and the most interesting hits were verified by ChIP-PCR and STAT3 knockdown in human glioma cells.CONCLUSIONS: Non-random association between silent genes, histone marks and p-Stat3 binding near transcription start sites was observed, consistent with its repressive role in transcriptional regulation of target genes in glioma cells with specific genetic background.
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| 6. |
- Köhler, Claudia
(författare)
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Epigenetic mechanisms in the endosperm and their consequences for the evolution of flowering plants
- 2011
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Ingår i: BBA - Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399 .- 1876-4320. ; 1809, s. 438-443
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Tidskriftsartikel (refereegranskat)abstract
- The sudden rise of angiosperms to ecological dominance was an "abominable mystery" to Charles Darwin, and understanding the underlying evolutionary driving force has remained a scientific challenge since then. The recognition of polyploidization as an important factor for plant speciation is likely to hold a key to this mystery and we will discuss possible mechanisms underlying this phenomenon. Polyploidization raises an immediate reproductive barrier in the endosperm, pointing towards an important but greatly underestimated role of the endosperm in preventing interploidy hybridizations. Parent-of-origin-specific gene expression is largely restricted to the endosperm, providing an explanation for the dosage sensitivity of the endosperm. Here, we review epigenetic mechanisms causing endosperm dosage sensitivity, their possible consequences for raising interploidy and interspecies hybridization barriers and their impact on flowering plant evolution. This article is part of a Special Issue entitled: Epigenetic Control. (C) 2011 Elsevier B.V. All rights reserved.
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| 7. |
- Stec-Dziedzic, Ewa, et al.
(författare)
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Characterization of the transcriptional stimulatory properties of the Pseudomonas putida RapA protein
- 2013
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Ingår i: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399 .- 1876-4320. ; 1829:2, s. 219-230
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Tidskriftsartikel (refereegranskat)abstract
- RNA polymerase-associated factors can significantly affect its performance at specific promoters. Here we identified a Pseudomonas putida RNA polymerases-associated protein as a homolog of Escherichia coli RapA. We found that P. putida RapA stimulates the transcription from promoters dependent on a variety of sigma-factors (sigma(70), sigma(S), sigma(54), sigma(32), sigma(E)) in vitro. The level of stimulation varied from 2- to 10-fold, with the maximal effect observed with the sigma(E)-dependent PhtrA promoter. Stimulation by RapA was apparent in the multi-round reactions and was modulated by salt concentration in vitro. However, in contrast to findings with E. coli RapA, P. putida RapA-mediated stimulation of transcription was also evident using linear templates. These properties of P. putida RapA were apparent using either E. coli- or P. putida-derived RNA polymerases. Analysis of individual steps of transcription revealed that P. putida RapA enhances the stability of competitor-resistant open-complexes formed by RNA polymerase at promoters. In vivo, P. putida RapA can complement the inhibitory effect of high salt on growth of an E. coli RapA null strain. However, a P. putida RapA null mutant was not sensitive to high salt. The in vivo effects of lack of RapA were only detectable for the sigma(E)-PhtrA promoter where the RapA-deficiency resulted in lower activity. The presented characteristics of P. putida RapA indicate that its functions may extend beyond a role in facilitating RNA polymerase recycling to include a role in transcription initiation efficiency.
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| 8. |
- Szilagyi, Zsolt, et al.
(författare)
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Emerging roles of Cdk8 in cell cycle control
- 2013
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Ingår i: Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399. ; 1829:9, s. 916-920
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Tidskriftsartikel (refereegranskat)abstract
- Cyclin dependent kinase 8 (Cdk8) is a component of Mediator, an evolutionary conserved multiprotein complex that regulates RNA polymerase II-dependent transcription. Cdk8 has been implicated as a regulator of multiple steps in cell cycle progression. We here discuss recent advances in our understanding of Cdk8 function and a possible role for Mediator as a hub for integrating transcription regulation with cell cycle progression. (c) 2013 Elsevier B.V. All rights reserved.
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| 9. |
- Veide Vilg, Jenny, 1973, et al.
(författare)
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Elucidating the response of Kluyveromyces lactis to arsenite and peroxide stress and the role of the transcription factor KlYap8.
- 2014
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Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1839:11, s. 1295-1306
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Tidskriftsartikel (refereegranskat)abstract
- All organisms need to sense and respond to a range of stress conditions. In this study, we used transcriptional profiling to identify genes and cellular processes that are responsive during arsenite and tert-butyl hydroperoxide exposure in Kluyveromyces lactis. Many arsenite-responsive genes encode proteins involved in redox processes, protein folding and stabilization, and transmembrane transport. The majority of peroxide-responsive genes encode functions related to transcription, translation, redox processes, metabolism and transport. A substantial number of these stress-regulated genes contain binding motifs for the AP-1 like transcription factors KlYap1 and KlYap8. We demonstrate that KlYap8 binds to and regulates gene expression through a 13 base-pair promoter motif, and that KlYap8 provides protection against arsenite, antimonite, cadmium and peroxide toxicity. Direct transport assays show that Klyap8Δ cells accumulate more arsenic and cadmium than wild type cells and that the Klyap8Δ mutant is defective in arsenic and cadmium export. KlYap8 regulates gene expression in response to both arsenite and peroxide, and might cooperate with KlYap1 in regulation of specific gene targets. Comparison of KlYap8 with its Saccharomyces cerevisiae orthologue ScYap8 indicates that KlYap8 senses and responds to multiple stress signals whereas ScYap8 is only involved in the response to arsenite and antimonite. Thus, our data suggest that functional specialization of ScYap8 has occurred after the whole genome duplication event. This is the first genome-wide stress response analysis in K. lactis and the first demonstration of KlYap8 function.
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