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Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67485 | GEO | 2015/06/16

SECONDARY ACCESSION(S): PRJNA280050

REPOSITORIES: GEO

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Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-06-16 | E-GEOD-67485 | biostudies-arrayexpress

Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme [I]

Project description:In order to elucidate the role of DNA methylation in the DME gene regulation, global DNA methylation and mRNA expression profiles of human tissues and cell lines were examinde by HumanMethylation450 Bead Chip and SurePrint G3 Human Gene Expression 8×60K v2. We demonstrated DNA methylation landscape of the DME genes in human tissues. Although a fraction of DME genes can be regulated by their DNA methylation, the variable DNA methylation status probably affects drug metabolism and response. Total RNA was isolated from 2 human tissues (liver and small intestine) and 3 human hepatoma cells that were treated with or without 5-aza-2’-deoxycytidine, and used for mRNA expression analysis.

2015-06-16 | E-GEOD-67318 | biostudies-arrayexpress

Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme [III]

Project description:In order to elucidate the role of DNA methylation in the DME gene regulation, global DNA methylation and mRNA expression profiles of human tissues and cell lines were examinde by HumanMethylation450 Bead Chip and SurePrint G3 Human Gene Expression 8×60K v2. We demonstrated DNA methylation landscape of the DME genes in human tissues. Although a fraction of DME genes can be regulated by their DNA methylation, the variable DNA methylation status probably affects drug metabolism and response. Bisulphite converted DNA from the 4 samples were hybridized to the Illumina HumanMethylation450 BeadChip (Sample L and SI were examined twice).

2015-06-16 | E-GEOD-67484 | biostudies-arrayexpress

Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme [II]

Project description:In order to elucidate the role of DNA methylation in the DME gene regulation, global DNA methylation and mRNA expression profiles of human tissues and cell lines were examinde by HumanMethylation450 Bead Chip and SurePrint G3 Human Gene Expression 8×60K v2. We demonstrated DNA methylation landscape of the DME genes in human tissues. Although a fraction of DME genes can be regulated by their DNA methylation, the variable DNA methylation status probably affects drug metabolism and response. Bisulphite converted DNA from the 7 samples were hybridized to the Illumina HumanMethylation450 BeadChip.

2015-06-16 | E-GEOD-67477 | biostudies-arrayexpress

Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme [III]

2015-06-16 | GSE67484 | GEO

Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme [II]

2015-06-16 | GSE67477 | GEO

Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme [I]

2015-06-16 | GSE67318 | GEO

Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme

Project description:Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme

| PRJNA280050 | ENA

Analysis of DNA methylation landscape reveals the roles of DNA methylation in the regulation of drug metabolizing enzymes.

Project description:BACKGROUND: Drug metabolizing enzymes (DMEs) exhibit dramatic inter- and intra-individual variability in expression and activity. However, the mechanisms determining this variability have not been fully elucidated. The aim of this study was to evaluate the biological significance of DNA methylation in the regulation of DME genes by genome-wide integrative analysis. RESULTS: DNA methylation and mRNA expression profiles of human tissues and hepatoma cells were examined by microarrays. The data were combined with GEO datasets of liver tissues, and integrative analysis was performed on selected DME genes. Detailed DNA methylation statuses at individual CpG sites were evaluated by DNA methylation mapping. From analysis of 20 liver tissues, highly variable DNA methylation was observed in 37 DME genes, 7 of which showed significant inverse correlations between DNA methylation and mRNA expression. In hepatoma cells, treatment with a demethylating agent resulted in upregulation of 5 DME genes, which could be explained by DNA methylation status. Interestingly, some DMEs were suggested to act as tumor-suppressor or housekeeper based on their unique DNA methylation features. Moreover, tissue-specific and age-dependent expression of UDP-glucuronosyltransferase 1A splicing variants was associated with DNA methylation status of individual first exons. CONCLUSIONS: Some DME genes were regulated by DNA methylation, potentially resulting in inter- and intra-individual differences in drug metabolism. Analysis of DNA methylation landscape facilitated elucidation of the role of DNA methylation in the regulation of DME genes, such as mediator of inter-individual variability, guide for correct alternative splicing, and potential tumor-suppressor or housekeeper.

| S-EPMC4587720 | biostudies-literature

GPER is involved in the regulation of the estrogen-metabolizing CYP1B1 enzyme in breast cancer.

Project description:The cytochrome P450 1B1 (CYP1B1) is a heme-thiolate monooxygenase involved in both estrogen biosynthesis and metabolism. For instance, CYP1B1 catalyzes the hydroxylation of E2 leading to the production of 4-hydroxyestradiol that may act as a potent carcinogenic agent. In addition, CYP1B1 is overexpressed in different tumors including breast cancer. In this scenario, it is worth mentioning that CYP1B1 expression is triggered by estrogens through the estrogen receptor (ER)α in breast cancer cells. In the present study, we evaluated whether the G protein estrogen receptor namely GPER may provide an alternate route toward the expression and function of CYP1B1 in ER-negative breast cancer cells, in main players of the tumor microenvironment as cancer associated fibroblasts (CAFs) that were obtained from breast cancer patients, in CAFs derived from a cutaneous metastasis of an invasive mammary ductal carcinoma and in breast tumor xenografts. Our results show that GPER along with the EGFR/ERK/c-Fos transduction pathway can lead to CYP1B1 regulation through the involvement of a half-ERE sequence located within the CYP1B1 promoter region. As a biological counterpart, we found that both GPER and CYP1B1 mediate growth effects in vitro and in vivo. Altogether, our data suggest that estrogens in ER-negative cell contexts may engage the alternate GPER signaling toward CYP1B1 regulation. Estrogen-CYP1B1 landscape via GPER should be taken into account in setting novel pharmacological approaches targeting breast cancer development.

| S-EPMC5739760 | biostudies-literature

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