RSAT: regulatory sequence analysis tools

Thomas‐Chollier, Morgane; Sand, Olivier; Turatsinze, Jean Valéry; Janky, Rekin’s; Defrance, Matthieu; Vervisch, Eric; Brohée, Sylvain; Helden, Jacques van

doi:10.1093/nar/gkn304

Cited by 248 publications

(243 citation statements)

References 31 publications

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“…yeastgemome.org). Candidate binding motifs in a given set of genes for transcriptional factors were identified using regulatory sequence analysis (RSA) tools [71,73]. Five to eight oligonucleotide sizes in the promoter regions of genes were chosen while searching for transcription factor binding motifs.…”

Section: Synthesis Of 56messmentioning

confidence: 99%

Identification of the molecular mechanisms underlying the cytotoxic action of a potent platinum metallointercalator

et al. 2011

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Platinum-based DNA metallointercalators are structurally different from the covalent DNA binders such as cisplatin and its derivatives but have potent in vitro activity in cancer cell lines. However, limited understanding of their molecular mechanisms of cytotoxic action greatly hinders their further development as anticancer agents. In this study, a lead platinum-based metallointercalator, [(5,6-dimethyl-1,10-phenanthroline) (1S,2S-diaminocyclohexane) platinum(II)] 2+ (56MESS) was found to be 163-fold more active than cisplatin in a cisplatin-resistant cancer cell line. By using transcriptomics in a eukaryotic model organism, yeast Saccharomyces cerevisiae, we identified 93 genes that changed their expressions significantly upon exposure of 56MESS in comparison to untreated controls (p≤0.05). Bioinformatic analysis of these genes demonstrated that iron and copper metabolism, sulfur-containing amino acids and stress response were involved in the cytotoxicity of 56MESS. Follow-up experiments showed that the iron and copper concentrations were much lower in 56MESS-treated cells compared to controls as measured by inductively coupled plasma optical emission spectrometry. Deletion mutants of the key genes in the iron and copper metabolism pathway and glutathione synthesis were sensitive to 56MESS. Taken together, the study demonstrated that the cytotoxic action of 56MESS is mediated by its ability to disrupt iron and copper metabolism, suppress the biosynthesis of sulfur-containing amino acids and attenuate cellular defence capacity. As these mechanisms are in clear contrast to the DNA binding mechanism for cisplatin and its derivative, 56MESS may be able to overcome cisplatinresistant cancers. These findings have provided basis to further develop the platinum-based metallointercalators as anticancer agents.

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Section: Synthesis Of 56messmentioning

confidence: 99%

Identification of the molecular mechanisms underlying the cytotoxic action of a potent platinum metallointercalator

et al. 2011

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“…In this regard, oligo-analysis in Regulatory Sequence Analysis Tools (RSAT; http://rsat. ulb.ac.be/rsat/) (Thomas-Chollier et al 2008) was used to search for 8-bp sequences that were significantly overrepresented in the promoter regions of genes in this cluster (see Materials and methods for details). The results showed that two motifs, AAAATATC and AAATATCT, were over-represented.…”

Section: Known and Potential Cis-elementsmentioning

confidence: 99%

Transcriptomic response of Arabidopsis thaliana to tunicamycin-induced endoplasmic reticulum stress

Iwata

Sakiyama

Lee

et al. 2010

Plant Biotechnology

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“…Sequence alignments were performed using Clustal W. Consensus sequence analysis was performed using the regulatory sequence analysis tool (Thomas-Chollier et al, 2008). Binding constants were determined by regression analysis using Sigmaplot 12.0.…”

Section: Discussionmentioning

confidence: 99%

In-vitro Characterization of an L-Kynurenine-Responsive Transcription Regulator of the Oxidative Tryptophan Degradation Pathway in Burkholderia xenovorans

Hall¹,

Martí‐Arbona²,

Hennelly³

et al. 2013

JMBR

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To study the transcriptional regulation of oxidative tryptophan degradation in Burkholderia, we used comparative genomics that focused on the operon containing the genes annotated as kynA, kynU and kynB. In all sequenced β-proteobacteria to-date, including Burkholderia, Ralstonia, Collimonas, and Cupriavidus species, there is a conserved AsnC/Lrp family transcriptional regulator (TR) gene located upstream and in the opposite strand of the operon encoding for the oxidative tryptophan degradation genes. In Burkholderia xenovorans the TR is Bxe_A0736. GST-Bxe_A0736 binds L-kynurenine with greater affinity and specificity than any other amino acid or tryptophan degradation product with a dissociation constant of ~82 ± 11 μM. DNaseI footprinting suggested that Bxe_A0736 protects a set of four degenerate, palindromic sequences within the intergenic region between Bxe_A0735 (kynB) and Bxe_A0736. The optimal consensus sequence obtained by analysis for these sites, ATATTCCGAATAT, closely resembles the sequence obtained with a protein binding microarray. Under our fluorescence anisotropy experimental conditions, 1 mM L-kynurenine increased the affinity of Bxe_A0736 for a portion of its promoter region. Our results are consistent with Bxe_A0736 acting as the TR that promotes the transcription of the oxidative tryptophan degradation genes in the presence of L-kynurenine while inhibiting the transcription of its own gene.

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RSAT: regulatory sequence analysis tools

Cited by 248 publications

References 31 publications

Identification of the molecular mechanisms underlying the cytotoxic action of a potent platinum metallointercalator

Identification of the molecular mechanisms underlying the cytotoxic action of a potent platinum metallointercalator

Transcriptomic response of Arabidopsis thaliana to tunicamycin-induced endoplasmic reticulum stress

In-vitro Characterization of an L-Kynurenine-Responsive Transcription Regulator of the Oxidative Tryptophan Degradation Pathway in Burkholderia xenovorans

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