Dataset Information

Quantification of gene-specific methylation of DNMT3B and MTHFR using sequenom EpiTYPER®.

ABSTRACT: Among 272 patients undergoing a screening colonoscopy, DNA methylation of DNMT3B and MTHFR, genes encoding enzymes critical to one-carbon metabolism, was quantified in blood leukocytes using Sequenom EpiTYPER®. DNA methylation was quantified in 66 and 28 CpG sites of DNMT3B and MTHFR respectively, and conceptualized using two approaches. First, measures representing average methylation across all CpG sites were created. Second, unsupervised principal component (PC) analysis was used as a pattern derivation and data-reduction approach, to develop two summary variables (PC1 and PC2). These two summary variables represented methylation around the transcription start site (PC1) and in the gene-coding area (PC2) for both DNMT3B and MTHFR. The data contained in this article presents the variation of methylation levels for individual CpG sites within the DNMT3B and MTHFR genes and possible correlations uncovered using PC analysis. The data are related to the research article "Gene-specific DNA methylation of DNMT3B and MTHFR and colorectal adenoma risk" in Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis.

SUBMITTER: Ho V

PROVIDER: S-EPMC4683340 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Quantification of gene-specific methylation of DNMT3B and MTHFR using sequenom EpiTYPER®.

Ho Vikki V Ashbury Janet E JE Taylor Sherryl S Vanner Stephen S King Will D WD

Data in brief 20151126

Among 272 patients undergoing a screening colonoscopy, DNA methylation of DNMT3B and MTHFR, genes encoding enzymes critical to one-carbon metabolism, was quantified in blood leukocytes using Sequenom EpiTYPER®. DNA methylation was quantified in 66 and 28 CpG sites of DNMT3B and MTHFR respectively, and conceptualized using two approaches. First, measures representing average methylation across all CpG sites were created. Second, unsupervised principal component (PC) analysis was used as a pattern ...[more]

PMID: 26759827

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Project description:Both DNA methylation and alternative splicing represent mechanisms closely involved in regulation of gene expression and are well known to be involved in cancer susceptibility and development. Human DNA methylation is introduced into DNA by enzymes of the DNA cytosine methyltransferases family, which includes DNMT3B. The DNMT3B protein allows a de novo DNA methylation activity, which is a key mechanism involved in the transformation of normal cell into cancer cell. The DNMT3B3 isoform is overexpressed in cancerous tissues and tumor cell lines, and could act as a dominant negative factor. This isoform was found to be highly expressed in our cohort of non-BRCA1/2 families. Using Infinium Human Methylation 450 BeadChips, we undertook the characterization of the specific methylation profile associated with this DNMT3B3 isoform and its DNMT3B2 wild type counterpart in ER/PR-positive and –negative breast cancer cell lines. A large spectrum of DNMT3B3/DNMT3B2 expression ratio values was observed in cancer and non-cancerous cell lines. Based on their methylation profiles, hierarchical clustering of parental cell lines revealed clustering of cells based on their ER/PR status. Overexpression of DNMT3B3 triggered methylation changes of thousands of CpG sites in MCF7, T-47D, MDA-MB-231 and MCF10A cells. These methylated loci were distributed in similar proportion over the 22 autosomal chromosomes and genomic locations such as promoter, gene body or intergenic regions. Pathways associated with genes containing these differentially methylated CpG sites were also determined regarding their enrichment. Moreover, based on the trend of methylation changes, the results suggest an anti-proliferative effect of the DNMT3B3 isoform through negative effect on its wild-type isoform counterpart DNMT3B2. To our knowledge, this study represents the first exhaustive analysis describing specific methylation profile triggered by modulated expression of DNMT3B isoforms and revealed specific genes and pathways, which could significantly regulate cell growth and proliferation as well as other biological and molecular mechanisms.

Dataset Information

Quantification of gene-specific methylation of DNMT3B and MTHFR using sequenom EpiTYPER®.

Publications

Quantification of gene-specific methylation of DNMT3B and MTHFR using sequenom EpiTYPER®.

Similar Datasets

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