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| Status |
Public on Feb 10, 2016 |
| Title |
Histone H3 lysine 4 acetylation-methylation dynamics define breast cancer subtypes [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The onset and progression of breast cancer are linked to genetic and epigenetic changes that alter the normal programming of cells. Epigenetic modifications of DNA and histones contribute to chromatin structure that results in the activation or repression of gene expression. Several epigenetic pathways have been shown to be highly deregulated in cancer cells. Targeting specific histone modifications represents a viable strategy to prevent oncogenic transformation, tumor growth or metastasis. Methylation of histone H3 lysine 4 has been extensively studied and shown to mark genes for expression; however this residue can also be acetylated and the specific function of this alteration is less well known. To define the relative roles of histone H3 methylation (H3K4me3) and acetylation (H3K4ac) in breast cancer, we determined genomic regions enriched for both marks in normal-like (MCF10A), transformed (MCF7) and metastatic (MDA-MB-231) cells using a genome-wide ChIP-Seq approach. Our data revealed a genome-wide gain of H3K4ac associated with both early and late breast cancer cell phenotypes, while gain of H3K4me3 was predominantly associated with late stage cancer cells. Enrichment of H3K4ac was overrepresented at promoters of genes associated with cancer-related phenotypic traits, such as estrogen response and epithelial-to-mesenchymal transition pathways. Our findings highlight an important role for H3K4ac in predicting epigenetic changes associated with early stages of transformation. In addition, our data provide a valuable resource for understanding epigenetic signatures that correlate with known breast cancer-associated oncogenic pathways.
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| |
|
| Overall design |
RNA-Seq of cell lines MCF10A, MCF7 and MDA-MB-231.
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| |
|
| Contributor(s) |
Messier T, Jonathan G, Boyd J, Tye C, Browne G, Stein J, Lian J, Stein G |
| Citation(s) |
26783963 |
| |
| Submission date |
Nov 18, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Jonathan AR Gordon |
| E-mail(s) |
Jonathan.A.Gordon@uvm.edu
|
| Organization name |
University of Vermont
|
| Department |
Biochemistry
|
| Street address |
89 Beaumont Ave Given E209
|
| City |
Burlington |
| State/province |
VT |
| ZIP/Postal code |
05405 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
|
| Samples (9)
|
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| This SubSeries is part of SuperSeries: |
| GSE75169 |
Histone H3 Lysine4 Acetylation-Methylation Dynamics Define Breast Cancer Subtypes |
|
| Relations |
| BioProject |
PRJNA302668 |
| SRA |
SRP066387 |
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