Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression analysis of the colon with and without DNA methyltransferase 1 (Dnmt1) inhibition

ABSTRACT: We performed gene expression microarray to assess the effects of reduced DNA methylation on global gene expression. Gene expression profiles of colonic mucosa from mice with two different genotypes (Dnmt1LO/LO and Dnmt1LO/LO, TgVillacIGY) were compared. Dnmt1 expression is repressed only in the Dnmt1LO/LO, TgVillacIGY mice. Total RNA was isolated from the colonic mucosa of four mouse, two biological replicates of each genotype in two technical relicates. Their gene expression profiles were obtained using the Illumina Ref-8 whole-genome expression BeadChip (MouseRef-8 v2.0). We processed our data using the Lumi Id and ReMOAT annotation data base (MouseWG-6 corresponding to GPL6887).

ORGANISM(S): Mus musculus

SUBMITTER: KwangHo Lee

PROVIDER: E-GEOD-28386 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. We assessed the impact of prenatal exposure to arsenic on genome-wide miRNA expression profiles and their potential influence on gene expression patterns in the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort. This cohort includes residents from Gómez Palacio, located in the state of Durango in the Lagunera region of Northern Mexico. A total of 200 pregnant women residing in Gómez Palacio, State of Durango, Mexico, were recruited at the General Hospital of Gómez Palacio to participate in the BEAR prospective pregnancy cohort. The present study focuses on miRNA expression profiles and utilizes 40 samples obtained from mother-newborn pairs selected from the larger cohort (n=200). The subcohort was selected to include subjects exposed to varying levels of arsenic as determined by both total arsenic in maternal urine (U-tAs) and inorganic arsenic in drinking water (DW-iAs). Cord blood samples were collected from the newborns immediately after infant delivery. Blood samples were collected using PreAnalytix PaxGene RNA tubes and extracted using the PAXgene RNA Kit, per standard protocol (Qiagen, Valencia, CA). Isolated RNA used for microarray analysis were amplified and labeled using the NuGEN Ovation Pico WTA System V2 and Encore Biotin Module, respectively (NuGEN, San Carlos, CA). RNA isolated from 40 cord blood samples were labeled and hybridized to the Agilent Human miRNA Microarray, based off miRBase v16.0.

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Gene expression analysis of the colon with and without DNA methyltransferase 1 (Dnmt1) inhibition

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