Abstract
To investigate the effect of TIEG-siRNA on Smad2, p-smad2 and collagen IV in diabetic nephropathy rats induced by streptozotocin (STZ).
Ten Sprague-Dawley rats injected with STZ were randomly divided into TIEG-siRNA and Control groups. Other five normal rats were used as control. Each of the TIEG-si...
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PMID: 20979836
PDF is available here.
Abstract
We show that variegated CD8 expression by loss of Cd8 enhancers was reverted in MAZR-deficient mice, which confirms that MAZR negatively regulates the Cd8 loci during the transition to the double-positive (DP) stage. Moreover, loss of MAZR led to partial redirection of major histocompatibility compl...
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PMID: 20383150
PDF is available here.
Abstract
Insulators are cis-regulatory elements that prevent improper gene activation and heterochromatin spreading. An insulator is contained in the Mcp boundary from the regulatory region of the Drosophila melanogaster Abd-B gene. The barrier function of the Mcp insulator was studied and proved to be due t...
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PMID: 20583593
PDF is available here.
Abstract
We reviewed the epigenetic modifications involved in the induction of human brain tumors, particularly focusing on polycomb-repressive complex-mediated histone (H3) lysine (K) 27 tri-methylation (K27-3Me) and other DNA methylation patterns, which are known to act as transcriptional silencing machine...
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PMID: 19618856
PDF is available here.
Abstract
We reviewed the epigenetic modifications involved in the induction of human brain tumors, particularly focusing on polycomb-repressive complex-mediated histone (H3) lysine (K) 27 tri-methylation (K27-3Me) and other DNA methylation patterns, which are known to act as transcriptional silencing machine...
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PMID: 19618856
PDF is available here.
Abstract
We show that nucleosomes at the CD4 silencer occupy multiple translational frames. BAF57 dominant negative mutant does not alter these frames, but reduces the accessibility of the entire silencer without affecting the flanking regions, concomitant with localized accumulation of linker histone H1 and...
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PMID: 19180471
PDF is available here.
Abstract
We sought to clarify the in vivo role of two elements, termed Enh and F, located 3' to the Agamma-globin, in silencing the fetal genes. To this end, we generated three transgenic lines using cosmid constructs containing the full length of the globin locus control region (LCR) linked to the 3.3-kb Ag...
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PMID: 19690621
PDF is available here.
Abstract
A candidate cis-acting exonic splicing silencer (ESS) comprising nucleotides 22-30 of exon 6A sequence was identified corresponding to the a silencer consensus sequence of AAGGGG. The function of this sequence as an ESS was confirmed in vivo both in the context of the reporter minigene as a plasmid...
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PMID: 19922608
PDF is available here.
Abstract
We used chromatin immunoprecipitation to compare the rates of Sir protein assembly at different genomic locations and discovered that establishment of silenced chromatin was much more rapid at HMR than at the telomere VI-R. Silenced chromatin also assembled more quickly on one side of HMR-E than on...
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PMID: 18955502
PDF is available here.
Abstract
We showed that inefficient upregulation of ThPOK, induced by removal of the proximal enhancer from the ThPOK locus, resulted in the transdifferentiation of helper lineage-specified cells into the cytotoxic T cell lineage. Furthermore, direct antagonism by ThPOK of the Cd4 and ThPOK silencers generat...
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PMID: 18776907
PDF is available here.
Abstract
We report here a novel strategy used by a single splicing regulator that blocks the formation of two distinct prespliceosome complexes to achieve efficient regulation. Fox-1/Fox-2 proteins, potent regulators of alternative splicing in the heart, skeletal muscle, and brain, repress calcitonin-specifi...
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PMID: 18573872
PDF is available here.
Abstract
Adding to the concept that Mediator acts as an "integrative hub,"Ding et al. (2008) report in this issue of Molecular Cell that, by facilitating the recruitment of the G9a methyl transferase, Mediator can also promote epigenetic silencing of selected genes.
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PMID: 18691961
PDF is available here.
Abstract
We describe a protein interaction network required for extraneuronal gene silencing comprising Mediator, G9a histone methyltransferase, and the RE1 silencing transcription factor (REST; also known as neuron restrictive silencer factor, NRSF). We show that the MED12 interface in Mediator links REST w...
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PMID: 18691967
PDF is available here.
Abstract
We developed an experimental strategy to identify silencers and EBs using transient transfection assays. A known insulator and EB from the chicken beta-globin locus, cHS4, served as a control element for these assays. We examined 47 sequences from a 1.8-Mb region of human chromosome 7 for silencer a...
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PMID: 18436892
PDF is available here.
Abstract
These results indicate that silencing SOCS gene expression can be an effective strategy to enhance the antitumor effect of IFN under conditions in which the SOCS gene expression is upregulated by IFN....
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PMID: 18754879
PDF is available here.
Abstract
We performed a comprehensive linker scan analysis of ARS318. Unexpectedly, this replicator depends on a 9/11-bp match to the ACS that positions the ORC binding site only 6 bp away from an Abf1p binding site. Although a largely inactive replicator on the chromosome, ARS318 becomes active if the nearb...
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PMID: 18573888
PDF is available here.
Abstract
We study SI 62D and show that interactions occur between two SI 62D elements, but not between SI 62D and the gypsy insulator, limiting the scope of genomic gypsy insulator interactions. Enhancer blocking by SI 62D requires fewer Su(Hw)-binding sites than needed for gypsy insulator function, with the...
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PMID: 18562648
PDF is available here.
Abstract
We studied a father and son in an Iranian-American family who had elevated Hb F levels and found a novel T-to-G transversion at nucleotide (nt) -567 of the HBG2 promoter. This mutation alters a GATA-1 binding motif to a GAGA sequence located within a previously identified silencing element. DNA-prot...
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PMID: 18443038
PDF is available here.
Micaela M Gallozzi,
Vincent V Béringue,
Pauline P Decaunes,
Annick A Le Dur,
Karine K Le Roux,
Gaëlle G Tilly,
Sandrine S Le Guillou,
Laetitia L Herzog,
Coralie C Peyre,
Aline A Ladroue,
Jérôme J Chapuis,
Marthe M Vilotte,
Bruno B Passet,
José J Costa,
Nathalie N Chenais,
Fabienne F Le Provost,
Hubert H Laude and
Jean-Luc JL Vilotte
Abstract
Spatial and temporal control of ovine prion protein (Prnp) gene expression was achieved in mice using two transgenes: a Prnp minigene with tet-operator sequences inserted 5' to exon 1 and a mouse neurofilament genomic clone carrying the chimeric-repressor TRSID cDNA. In bi-transgenic mice, ovine PrP...
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PMID: 18501713
PDF is available here.
Abstract
We summarize the current state of knowledge of splicing cis-regulatory elements and their context-dependent effects on splicing, emphasizing recent global/genome-wide studies and open questions....
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PMID: 18369186
PDF is available here.
Abstract
We explored the molecular mechanisms underlying this complex mode of regulation by examining the nucleoprotein structure of the CD4 locus throughout T cell development and in DN cells lacking the CD4 silencer. In DN cells, the CD4 enhancer is preloaded with multiple transcription activators, but p30...
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PMID: 18322012
PDF is available here.
Abstract
We investigate the regulation of ThPOK expression and its subsequent control of CD4+ T cell commitment. Treatment of immature thymocytes with anti-TCR (T cell receptor) showed that TCR signals were important in ThPOK induction and that the CD4+8lo stage was the likely target of the inductive TCR sig...
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PMID: 18342007
PDF is available here.
Abstract
We have developed a promoter-reporter gene assay using different cell lines. A 2047 base pairs (bp) human alphaCaMKII gene promoter was cloned from human genomic DNA. Unlike the rat alphaCaMKII promoter, DNA sequence analysis showed that the human promoter was devoid of TATA element. We made series...
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PMID: 17221287
PDF is available here.
Abstract
We report the redirected differentiation of class I-restricted thymocytes into CD4+CD8- helper-like T cells upon loss of Runx transcription factor complexes. A Runx-binding sequence within the Th-POK locus acts as a transcriptional silencer that is essential for Th-POK repression and for development...
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PMID: 18258917
PDF is available here.
Abstract
Silencing of the mating-type locus HMR in Saccharomyces cerevisiae requires DNA elements called silencers. To establish HMR silencing, the origin recognition complex binds the HMR-E silencer and recruits the silent information regulator (Sir)1 protein. Sir1 in turn helps establish silencing by stabi...
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PMID: 18045995
PDF is available here.
Abstract
We study the role of this 2 kb fragment in the regulation of the engrailed gene itself. Our results show that within this 2 kb fragment, there are two subfragments that can act as PREs in embryos. In addition to their role in gene silencing, these two adjacent PRE fragments can facilitate the activa...
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PMID: 18199580
PDF is available here.
Abstract
We suggest an additional mechanism by which constitutively spliced exons become alternative cassette exons during evolution. We compiled a dataset of orthologous exons from human and mouse that are constitutively spliced in one species but alternatively spliced in the other. Examination of these exo...
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PMID: 18020709
PDF is available here.
Abstract
We analyzed the secondary structure context of experimentally determined splicing enhancer and silencer motifs in their natural pre-mRNA context. We found that these splicing motifs are significantly more single-stranded than controls. These findings were validated by transfection experiments, where...
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PMID: 18020710
PDF is available here.
Abstract
We revealed the antagonistic interplay between Ikaros and its associate the chromatin remodeler Mi-2beta during T cell development, as exemplified by the regulation of Cd4 expression. Loss of Ikaros or Mi-2beta led to activation or repression, respectively, of the Cd4 locus at inappropriate stages o...
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PMID: 17980631
PDF is available here.
Abstract
We also showed that Oct-1 binds to one of these elements. Thus, this investigation reveals that TPP II expression could be regulated through both positive and negative regulatory elements. Further studies are required to establish the involvement of different genetic elements, and how the interplay...
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PMID: 17343995
PDF is available here.
Abstract
We examine the (AC)n(AT)xTy motif residing -530 bp 5' upstream of the beta-globin gene in Chinese thalassaemic patients. This motif is a putative binding site for a repressor protein, termed beta protein 1 (BP1) (Berg et al., Nucleic Acids Res 1989;17:8833-8852). Variations in the (AC)n(AT)xTy repea...
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PMID: 17133428
PDF is available here.
Abstract
We present evidences showing that triethylene tetraamine facilitates the formation of G-quadruplex structure by the NHE III(1) element, and inhibits the expression of c-myc in HeLa cells....
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PMID: 17339229
PDF is available here.
Karsten Bork KB Nielsen,
Suzette S Sørensen,
Luca L Cartegni,
Thomas Juhl TJ Corydon,
Thomas Koed TK Doktor,
Lisbeth Dahl LD Schroeder,
Line Sinnathamby LS Reinert,
Orly O Elpeleg,
Adrian R AR Krainer,
Niels N Gregersen,
Jørgen J Kjems and
Brage Storstein BS Andresen
Abstract
We use patient cells, model minigenes, and in vitro assays to show that a missense mutation in exon 5 of the medium-chain acyl-CoA dehydrogenase (MCAD) gene primarily causes exon skipping by inactivating a crucial exonic splicing enhancer (ESE), thus leading to loss of a functional protein and to MC...
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PMID: 17273963
PDF is available here.
Anne L AL Hancock,
Keith W KW Brown,
Kim K Moorwood,
Hanlim H Moon,
Claes C Holmgren,
Sudhanshu H SH Mardikar,
Anthony R AR Dallosso,
Elena E Klenova,
Dmitri D Loukinov,
Rolf R Ohlsson,
Victor V VV Lobanenkov and
Karim K Malik
Abstract
We have shown previously that AWT1 and WT1-AS are functionally imprinted in human kidney. In the adult kidney, expression of both transcripts is restricted to the paternal allele, with the silent maternal allele retaining methylation at the WT1 antisense regulatory region (WT1 ARR). Here, we report...
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PMID: 17210670
PDF is available here.
Abstract
Apple chlorotic leaf spot virus (ACLSV) is the type species of the genus Trichovirus and its single-stranded, plus-sense RNA genome encodes a 216 kDa protein (P216) involved in replication, a 50 kDa movement protein (P50) and a 21 kDa coat protein (CP). In this study, it was investigated whether the...
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PMID: 17170464
PDF is available here.
Abstract
We speculated that the CD4 silencer, which operates in CD8+ T-cells to repress CD4 expression, could be responsible for CD4 repression in human lymphoid non-T-cells. To test this possibility, we used lentiviral vectors carrying CD4 regulatory sequences, with or without the silencer element, to expre...
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PMID: 16630660
PDF is available here.
Abstract
MicroRNAs are small, non-coding RNAs that regulate gene expression on post-transcriptional level. When included in RISC complex they bind to 3' UTR of target gene implicating inhibition of translation or mRNA degradation. Primary miRNA transcripts are several hundred nucleotides long, during maturat...
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PMID: 19024905
PDF is available here.
Abstract
Intron removal during pre-mRNA splicing in higher eukaryotes requires the accurate identification of the two splice sites at the ends of the exons, or exon definition. The sequences constituting the splice sites provide insufficient information to distinguish true splice sites from the greater numbe...
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PMID: 18380342
PDF is available here.
Abstract
Using computational analysis and exploiting the diversity of teleost genomes, we identified a cluster of highly conserved noncoding sequences surrounding the Six3 gene. Transgenesis in medaka fish demonstrates that these sequences have enhancer, silencer, and silencer blocker activities that are dif...
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PMID: 17617896
PDF is available here.
Abstract
We examine how Tra2 blocks splicing of the M1 intron from its own transcript. We identify an intronic splicing silencer (ISS) adjacent to the M1 branch point that is sufficient to confer Tra2-dependent repression on another RNA. The ISS was found to function independently of its position within the...
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PMID: 17101798
PDF is available here.
Abstract
We show that the murine ICR maintains this function when tested in an in vivo transgenic Drosophila assay in the absence of DNA methylation. Furthermore, the H19 ICR interacts distinctively with Drosophila promoters of different regulatory strengths. We also demonstrate that the comparable region up...
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PMID: 17016732
PDF is available here.
Abstract
We have identified a cis-acting RNA element required for regulated splicing of G6PD mRNA. Using transfection of G6PD RNA reporter constructs into rat hepatocytes, the cis-acting RNA element involved in this regulation was localized to nucleotides 43-72 of exon 12 in the G6PD mRNA. In in vitro splici...
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PMID: 16980303
PDF is available here.
Abstract
We show that alphabeta lineage thymocytes in mice lacking a functional pre-TCR undergo limited proliferation and fail to silence TCRgamma genes during development. Stimulation of pre-TCR-deficient immature thymocytes with anti-CD3 Abs does not directly down-regulate TCRgamma transcription but restor...
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PMID: 17056529
PDF is available here.
Abstract
We have designed a novel conditional transcription technology, which enables reversible induction, repression and adjustment of desired transgene expression using the clinically inert 6-hydroxy-nicotine (6HNic). The 6-hydroxy-nicotine oxidase (6HNO) repressor (HdnoR), which manages nicotine metaboli...
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PMID: 16962351
PDF is available here.
Abstract
We searched for novel polymorphisms in the neuron restrictive silencer element located in the BDNF promoter. Then, the effect of the Val66Met variant in determining age of onset was tested in a large sample of HD carriers by using a multivariate regression approach. The CAG repeat number accounted f...
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PMID: 16905325
PDF is available here.
Abstract
Alu family sequences are middle repetitive short interspersed elements (SINEs) dispersed throughout vertebrate genomes that can modulate gene transcription. The human (h) GH locus contains 44 complete and four partial Alu elements. An Sx Alu repeat lies in close proximity to the hGH-1 and hGH-2 gene...
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PMID: 16762973
PDF is available here.
Abstract
We demonstrate that chromatin plays a key role in determining the potency and directionality of silencers. We show that nucleosomes are asymmetrically distributed around the HML-I or HMR-E silencer so that a nucleosome is positioned close to the Abf1p side but not the ORC side of the silencer. This...
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PMID: 16908533
PDF is available here.
Abstract
We demonstrate that the activity of a silencer pertaining to its potency and directionality is dependent on its genomic position. The context of the HML-E silencer is more permissive to silencer function than that of HML-I or HMR-E, despite that HML-E and HML-I are only 3.3 kb apart. The apparent st...
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PMID: 16783020
PDF is available here.
Abstract
Investigation of protein complexes, various types of protein modifications and the structure of the chromatin of specific chromosome regions, such as centromeres, telomeres, and adjacent heterochromatic regions, considerably complicated the notion on DNA, prevailing five decades ago, as molecules th...
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PMID: 17100088
PDF is available here.
Abstract
We describe the evidence for a parallel-stranded G-quadruplex in the purine-rich strand of the nuclease hypersensitivity element III(1) (NHE III(1)) of the promoter of c-MYC upstream of the P1 and P2 promoters. This biologically relevant G-quadruplex is a mixture of four loop isomers. The folding pa...
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PMID: 16890804
PDF is available here.
Abstract
We designed a new promoter that drives transgene expression in an exclusively neuron-specific manner. The promoter of superior cervical ganglion10 (SCG10), expressed in neurons, was further modified to enhance its neuron specificity and activity by changing its length and fusing a multiple neuronal...
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PMID: 16625241
PDF is available here.
Abstract
We report that suppression of GluR2 gene promoter activity is associated with kainate (KA)-induced downregulation of GluR2 subunit levels in primary cultured cortical neurons. RT-PCR and Northern blotting showed a significant decrease in GluR2 mRNA in cultured neurons after KA exposure. Transfection...
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PMID: 16701950
PDF is available here.
Abstract
We show here that the male germline is initiated by transcriptional control. We identify GRSF, germline-restrictive silencing factor, from the lily. GRSF is ubiquitous in nongerm cells and is absent from male germ cells. GRSF recognizes silencer sequences in promoters of genes specific to the germli...
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PMID: 16873660
PDF is available here.
Abstract
We find that almost all of a diverse panel of exonic splicing silencer (ESS) elements alter splice site choice when placed between competing sites, consistently inhibiting use of intron-proximal 5' and 3' splice sites. Supporting a general role for ESSs in splice site definition, we found that ESSs...
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PMID: 16797197
PDF is available here.
Abstract
We show that transcriptional start sites of the murine Bcl6 gene were different from the reported human one. DNA sequence around the new promoter region is highly conserved between mice and humans and has no canonical TATA or CCAAT box. Two AP-1-binding elements in the promoter region were the major...
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PMID: 16702165
PDF is available here.
Abstract
Epigenetic components drive the inheritance of transcriptional programs. This cellular memory is crucial for the stable maintenance of cell fates throughout development. Polycomb group (PcG) proteins are central players in various epigenetic phenomena, such as the maintenance of Hox expression patte...
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PMID: 16650749
PDF is available here.
Abstract
We investigated the effects of the neuroprotective drug, riluzole, on the GDNF gene expression in glial cells. Exposure of C6 glioma cells to riluzole (1 microM) significantly increased GDNF protein and mRNA levels. Using luciferase reporter gene constructs encoding fragments of the 5' untranslated...
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PMID: 16524382
PDF is available here.