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| Status |
Public on Sep 16, 2011 |
| Title |
Global DNA Hypomethylation Coupled to Repressive Chromatin Domain Formation and Gene Silencing in Breast Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
|
| Summary |
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.
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| |
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| Overall design |
Examination of histone modifications, DNA methylation, and gene expression in HCC1954 breast cancer cells and HMEC primary human mammary epithelial cells
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| |
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| Contributor(s) |
Hon GC, Ren B |
| Citation(s) |
22156296 |
| Submission date |
May 04, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Gary Chung Hon |
| Organization name |
UT Southwestern
|
| Department |
OB/GYN
|
| Street address |
5323 Harry Hines Blvd.
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (14)
|
| GSM721133 |
HCC1954: chromatin IP against H3K4me1 |
| GSM721134 |
HCC1954: chromatin IP against H3K4me3 |
| GSM721135 |
HCC1954: chromatin IP against H3K9me3 |
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| This SuperSeries is composed of the following SubSeries:
|
| GSE29118 |
Genome-wide location analysis in breast cancer cells (HCC1954) |
| GSE29119 |
Gene expression analysis of breast cancer (HCC1954) and normal breast cells (HMEC) |
| GSE29120 |
Bisulfite sequencing of ChIP DNA on breast cancer cells (HCC1954) |
| GSE29127 |
Genome-wide DNA methylation mapping in breast cancer cells (HCC1954) and normal breast cells (HMEC) |
|
| Relations |
| BioProject |
PRJNA140397 |
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