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Global DNA Hypomethylation Coupled to Repressive Chromatin Domain Formation and Gene Silencing in Breast Cancer

ABSTRACT: Global DNA Hypomethylation Coupled to Repressive Chromatin Domain Formation and Gene Silencing in Breast Cancer

OTHER RELATED OMICS DATASETS IN: GSE29069

PROVIDER: PRJNA140397 | ENA |

REPOSITORIES: ENA

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Global DNA Hypomethylation Coupled to Repressive Chromatin Domain Formation and Gene Silencing in Breast Cancer

Project description:While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation of tumor suppressors as well as changes in chromatin modifications as caused by genetic mutations of the chromatin-modifying machinery. However, the extent of epigenetic alterations in cancer cells has not been fully characterized. Here, we describe the first complete methylome maps at single nucleotide resolution of a low-passage breast cancer cell line and primary human mammary epithelial cells. We find widespread DNA hypomethylation in the cancer cell, primarily at partially methylated domains (PMDs) in normal breast cells. Unexpectedly, genes within these regions are largely silenced in cancer cells. The loss of DNA methylation in these regions is accompanied by formation of repressive chromatin, with a significant fraction displaying allelic DNA methylation where one allele is DNA methylated while the other allele is occupied by histone modifications H3K9me3 or H3K27me3. Our results show a mutually exclusive and complementary relationship between DNA methylation and H3K9me3 or H3K27me3. These results suggest that global DNA hypomethylation in breast cancer is tightly linked to the formation of repressive chromatin domains and gene silencing, thus identifying a potential epigenetic pathway for gene regulation in cancer cells and suggesting a possible new approach toward the development of cancer therapeutics. This SuperSeries is composed of the SubSeries listed below.

2011-09-16 | GSE29069 | GEO

Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer.

Project description: Not available

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Capturing the onset of PRC2-mediated repressive domain formation

Project description:Capturing the onset of PRC2-mediated repressive domain formation

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Capturing the onset of PRC2-mediated repressive domain formation

Project description:Our study defines nucleation and spreading regions for Polycomb repressive complex 2 (PRC2), demonstrating the principle of PRC2 domain formation in mammals. We elucidate the role of genome architecture in formation of these domains and identify JARID2 and MTF2 as being crucial for full recruitment of PRC2 to chromatin. This SuperSeries is composed of the SubSeries listed below.

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