Formation of Triple-stranded DNA at d(GA·TC)  Sequences Prevents Nucleosome Assembly and Is Hindered by Nucleosomes

Espinás, Maria Lluı̈sa; Jiménez-García, Emilio; Martinez-Balbas, A.; Azorı́n, Fernando

doi:10.1074/jbc.271.50.31807

Cited by 53 publications

(39 citation statements)

References 31 publications

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“…The selection between different homopurine-homopyrimidine DNA tracts on hTERT promoter was based on their chromatin organization and is supported by a number of researches both in vitro and in vivo, suggesting a decreased target accessibility to TFOs in the nucleosomal environment [29][30][31].…”

Section: Discussionmentioning

confidence: 97%

“…The single stranded TFO 13 and TFO 18 and the two strands forming DNA 30 and DNA 18 ( Figure 1b) were synthesized on a 15 μmol scale via the phosphoramidite method, using a PERSEPTIVE Biosystems synthesizer, purified by ionic exchange High Performance Liquid Chromatography (HPLC) and successively desalted by molecular exclusion chromatography (Biogel P-2 fine). The purity was checked by reverse phase HPLC and electrophoresis in 20% denaturing polyacrylamide gel containing 7 M urea.…”

Section: Oligonucleotides Synthesismentioning

confidence: 99%

“…In vivo chromosomal DNA is packaged by histone proteins into nucleosomes [28], so that the accessibility of TFO target sequences will be significantly decreased in chromatin with respect to naked DNA [29][30][31].…”

Section: Binding Affinity Of Tfos To the Selected Target Sequence On mentioning

confidence: 99%

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A model for triple helix formation on human telomerase reverse transcriptase (hTERT) promoter and stabilization by specific interactions with the water soluble perylene derivative, DAPER

Rossetti

D'Isa

Mauriello

et al. 2007

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Montesano 49, I-80131 Napoli, Italy. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT*corresponding author A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 2 ABSTRACTThe promoter of human telomerase reverse transcriptase (hTERT) gene, in the region from -1000 to +1, contains two homopurine-homopyrimidine sequences (-835/-814 and -108/-90), that can be considered as potential targets to triple helix forming oligonucleotides (TFOs) for applying antigene strategy.We have chosen the sequence (-108/-90) on the basis of its unfavorable Since DAPER is a symmetric molecule, the induced Circular Dichroism (CD) spectra in the range 400-600 nm, allows us to obtain information on drug binding to triplex and duplex DNA. The drug induced ellipticity is significantly higher in the case of triplex with respect to duplex and, surprisingly, it increases at decreasing of DNA. A model is proposed where self-stacked DAPER binds to triplex or to duplex narrow grooves.

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Section: Discussionmentioning

confidence: 97%

Section: Oligonucleotides Synthesismentioning

confidence: 99%

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A model for triple helix formation on human telomerase reverse transcriptase (hTERT) promoter and stabilization by specific interactions with the water soluble perylene derivative, DAPER

Rossetti

D'Isa

Mauriello

et al. 2007

Biophysical Chemistry

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“…However, in these studies, triplex formation with DNA in native chromatin structure was not unambiguous confirmed. In addition, some in vitro experiments indicate that chromatin structure is incompatible with triplex formation (356,394,395). Therefore, to clarify the accessibility of target sites in the context of chromatin is crucial for developing antigene strategies.…”

Section: 33mentioning

confidence: 99%

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

Houssein

Mahato

2007

Oligonucleotides

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Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of α1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed.

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“…These final 16 bp, however, were not sufficient for full initiation activity of an ori-beta mutant lacking the preceding repetitive sequences ( Figure 2D, 0.5DNR2 mutant). GA repeats have been shown to impede replication forks [37,47,48] and affect the assembly of DNA into nucleosomes [49], so both of these potential roles were investigated separately ( Figure 3). Importantly, a replication fork barrier (SB2) and an element that contains a nucleosomepositioning element (5S rDNA) were each able to independently replace the function of DNR ( Figure 3C).…”

Section: Transcription Factor Binding Sites Can Functionally Substitumentioning

confidence: 99%

Discrete functional elements required for initiation activity of the Chinese hamster dihydrofolate reductase origin beta at ectopic chromosomal sites

Gray

Liu

Altman

et al. 2007

Experimental Cell Research

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The Chinese hamster dihydrofolate reductase (DHFR) DNA replication initiation region, the 5.8 kb ori-beta, can function as a DNA replicator at random ectopic chromosomal sites in hamster cells. We report a detailed genetic analysis of the DiNucleotide Repeat (DNR) element, one of several sequence elements necessary for ectopic ori-beta activity. Deletions within ori-beta identified a 132 bp core region within the DNR element, consisting mainly of dinucleotide repeats, and a downstream region that are required for ori-beta initiation activity at non-specific ectopic sites in hamster cells. Replacement of the DNR element with Xenopus or mouse transcriptional elements from rDNA genes restored full levels of initiation activity, but replacement with a nucleosome positioning element or a viral intron sequence did not. The requirement for the DNR element and three other ori-beta sequence elements was conserved when ori-beta activity was tested at either random sites or at a single specific ectopic chromosomal site in human cells. These results confirm the importance of specific cis-acting elements in directing the initiation of DNA replication in mammalian cells, and provide new evidence that transcriptional elements can functionally substitute for one of these elements in ori-beta.

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Formation of Triple-stranded DNA at d(GA·TC) Sequences Prevents Nucleosome Assembly and Is Hindered by Nucleosomes

Abstract: Simple repeating d(GA⅐TC)n

Cited by 53 publications

References 31 publications

A model for triple helix formation on human telomerase reverse transcriptase (hTERT) promoter and stabilization by specific interactions with the water soluble perylene derivative, DAPER

A model for triple helix formation on human telomerase reverse transcriptase (hTERT) promoter and stabilization by specific interactions with the water soluble perylene derivative, DAPER

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

Discrete functional elements required for initiation activity of the Chinese hamster dihydrofolate reductase origin beta at ectopic chromosomal sites

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