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Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation [RNA-seq]

ABSTRACT: Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation [RNA-seq]

PROVIDER: PRJNA846768 | ENA |

REPOSITORIES: ENA

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Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation

Project description:Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation

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Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation [MethylationEPIC]

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Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation [MethylationEPIC]

Project description:DNA methylation is a fundamental epigenetic modification regulating gene expression. Aberrant DNA methylation is the most common molecular lesion in cancer cells. However, medical intervention has been limited to the use of broadly acting, small molecule-based demethylating drugs with significant side-effects and toxicities. To allow for targeted DNA demethylation, we integrated two novel nucleic acid-based approaches: DNMT1 interacting RNA (DiR) and RNA aptamer strategy. By combining the RNA inherent capabilities of inhibiting DNMT1 with an aptamer platform, we generated a first-in-class DNMT1-targeted approach – aptaDiR. Molecular modelling of RNA-DNMT1 complexes coupled with biochemical and cellular assays enabled the identification and characterization of aptaDiR. This novel RNA bio-drug blocked DNA methylation, impaired cancer cell viability and inhibited tumour growth in vivo. Collectively, we present an innovative RNA-based approach to modulate DNMT1 activity in cancer or diseases characterized by aberrant DNA methylation and suggest the first alternative strategy to overcome the limitations of currently approved hypomethylating protocols, which will greatly improve clinical intervention on DNA methylation

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Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation [RNA-seq]

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Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-11-22 | GSE205655 | GEO

An RNA-based platform to neutralize DNMT1 function AptaDiR is an innovative RNA-based platform to neutralize DNMT1 function

Project description:DNA methylation is a fundamental epigenetic modification regulating gene expression. Aberrant DNA methylation is the most common molecular lesion in cancer cells. However, medical intervention has been limited to the use of demethylating drugs that act indiscriminately on the genome and come with a toll of high toxicity and low specificity. Aptamers are novel targeting molecules considered high affinity ligands. By conjugating, the RNA inherent ability of inhibiting DNMT1, to an RNA aptamer platform, we generated the first-of-its kind aptamers approach targeting and neutralizing DNMT1 function – the aptaDiR. Molecular modelling of RNA-DNMT1 interactions’ coupled with biochemical and cellular assays enabled identification and characterization of the aptaDiR. This novel RNA bio-drug blocks DNA methylation and impairs cancer cell viability. Collectively, we present an innovative RNA-based approach to modulate DNMT1 activity in cancer or diseases characterized by aberrant DNA methylation and suggest the first alternative strategy to overcome the limitations of currently approved hypomethylating protocols which will greatly improve clinical intervention on DNA methylation.

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Systematic identification of metabolites controlling gene expression in E. coli

Project description:Systematic identification of metabolites controlling gene expression in E. coli

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An RNA-based platform to neutralize DNMT1 function AptaDiR is an innovative RNA-based platform to neutralize DNMT1 function

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RIPSEQ DNMT1 HL60

Project description:Identification of the all RNA species associated with DNMT1. Using a comparative genome-scale approach we identified and correlated the RNA species physically associated with DNMT1 and proximal to the annotated genes to the methylation status of the corresponding loci and expression levels of the respective genes. This comparative approach delineated the first -DNMT1 centered- 'epitranscriptome' map, a comprehensive map cross-referencing DNMT1-interacting transcripts to (i) DNA methylation and (ii) gene expression profile. Relationship between DNMT1-RNA interactions, DNA methylation and gene expression

2012-12-01 | E-GEOD-32162 | biostudies-arrayexpress

Conditional knockdown of DNA methyltransferase-1 (Dnmt1) reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis

Project description:To explore the epigenetic contribution to retinal development, we generated conditional knockout alleles of DNA methytransferase-1 (Dnmt1) mediated by Rx-Cre in mice. The results demonstrate a unique function of DNMT1-mediated DNA methylation in controlling RPE apicobasal polarity and neural retina differentiation. Retinal samples were harvested from both Dnmt1 mutant and wt animals at embryonic day 16.5 and postnatal days 0.5, 6.5, and 10.5 for microarray analysis. Each experiment was performed with biological quadruplicates. One microgram of total RNA was used for cDNA systhesis in target molecule production.

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