Department of Cell and Developmental Biology; Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Cancer Biology | Genomics | Molecular Biology | Systems Biology
BACKGROUND: Higher-order chromatin structure is often perturbed in cancer and other pathological states. Although several genetic and epigenetic differences have been charted between normal and breast cancer tissues, changes in higher-order chromatin organization during tumorigenesis have not been fully explored. To probe the differences in higher-order chromatin structure between mammary epithelial and breast cancer cells, we performed Hi-C analysis on MCF-10A mammary epithelial and MCF-7 breast cancer cell lines.
RESULTS: Our studies reveal that the small, gene-rich chromosomes chr16 through chr22 in the MCF-7 breast cancer genome display decreased interaction frequency with each other compared to the inter-chromosomal interaction frequency in the MCF-10A epithelial cells. Interestingly, this finding is associated with a higher occurrence of open compartments on chr16-22 in MCF-7 cells. Pathway analysis of the MCF-7 up-regulated genes located in altered compartment regions on chr16-22 reveals pathways related to repression of WNT signaling. There are also differences in intra-chromosomal interactions between the cell lines; telomeric and sub-telomeric regions in the MCF-10A cells display more frequent interactions than are observed in the MCF-7 cells.
CONCLUSIONS: We show evidence of an intricate relationship between chromosomal organization and gene expression between epithelial and breast cancer cells. Importantly, this work provides a genome-wide view of higher-order chromatin dynamics and a resource for studying higher-order chromatin interactions in two cell lines commonly used to study the progression of breast cancer.
DOI of Published Version
Genome Biol. 2015 Sep 28;16(1):214. doi: 10.1186/s13059-015-0768-0. Link to article on publisher's site
Barutcu, Ahmet Rasim; Lajoie, Bryan R.; McCord, Rachel Patton; Tye, Coralee E.; Hong, Deli; Messier, Terri L.; Browne, Gillian; van Wijnen, Andre J.; Lian, Jane B.; Stein, Janet L.; Dekker, Job; Imbalzano, Anthony N.; and Stein, Gary S., "Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells" (2015). Program in Systems Biology Publications and Presentations. 76.
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