Journal
EPIGENETICS
Volume 9, Issue 4, Pages 523-532Publisher
LANDES BIOSCIENCE
DOI: 10.4161/epi.27688
Keywords
differential gene expression; differential methylation; transcription factor; estrogen receptor alpha; breast cancer; DNase I hypersensitivity; ChIP-seq
Funding
- American Cancer Society Research Grant [IRG-82-003-27]
- Geisel School of Medicine at Dartmouth College
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Epigenetic modifications introduce an additional layer of regulation that drastically expands the instructional capability of the human genome. The regulatory consequences of DNA methylation is context dependent; it can induce, enhance, and suppress gene expression, or have no effect on gene regulation. Therefore, it is essential to account for the genomic location of its occurrence and the protein factors it associates with to improve our understanding of its function and effects. Here, we use ENCODE ChIP-seq and DNase I hypersensitivity data, along with large-scale breast cancer genomic data from The Cancer Genome Atlas (TCGA) to computationally dissect the intricacies of DNA methylation in regulation of cancer transcriptomes. In particular, we identified a relationship between estrogen receptor alpha (ER alpha) activity and DNA methylation patterning in breast cancer. We found compelling evidence that methylation status of DNA sequences at ER alpha binding sites is tightly coupled with ER alpha activity. Furthermore, we predicted several transcription factors including FOXA1, GATA1, and SUZ12 to be associated with breast cancer by examining the methylation status of their binding sites in breast cancer. Lastly, we determine that methylated CpGs highly correlated with gene expression are enriched in regions 1kb or more downstream of TSSs, suggesting more significant regulatory roles for CpGs distal to gene TSSs. Our study provides novel insights into the role of ER alpha in breast cancers.
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