Jun 18, 2017

Genome-wide methylome and chromatin interactome identify abnormal enhancer to be risk factor of breast cancer

Oncotarget
Yuan WangLi-Jun Di

Abstract

Enhancer is critical cis regulatory elements in gene expression. To understand whether and how the aberrant enhancer activation may contribute to cancer risk, the differentially methylated enhancers (eDMRs) in normal and malignant breast tissues were identified and analyzed. By incorporating genome-wide chromatin interaction, integrated analysis of eDMRs and target gene expression identified 1,272 enhancer-promoter pairs. Surprisingly, two functionally distinct groups of genes were identified in these pairs, one showing better correlation to enhancer methylation (eRGs) and the other showing better correlation to promoter methylation (pRGs), and the former group is functionally enriched with cancer related genes. Moreover, enhancer methylation based clustering of breast cancer samples is capable of discriminating basal breast cancer from other subtypes. By correlating enhancer methylation status to patient survival, 345 enhancers show the impact on the disease outcome and the majority of their target genes are important regulators of cell survival pathways including known cancer related genes. Together, these results suggest reactivation of enhancers in cancer cells has the add-on effect and contributes to cancer risk in combina...Continue Reading

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Citations

Mentioned in this Paper

Genome-Wide Association Study
Biochemical Pathway
Gene Expression Regulation, Neoplastic
Protein Methylation
Genome
Genes
Candidate Disease Gene
Methylate
DNA Methylation
Breast Tissue Sample

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