Abstract
BackgroundHigher-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.ResultsOur 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0768-0) contains supplementary material, which is available to authorized users.
Highlights
Higher-order chromatin structure is often perturbed in cancer and other pathological states
After sequence filtering [47], a total of ~152 and ~143 million interactions were obtained from the MCF-10A and MCF-7 combined replicate genome-wide chromosome conformation capture (Hi-C) libraries, respectively (Figure S1 in Additional file 1), with high reproducibility between the biological replicates (Figure S2 in Additional file 1)
Comparing the translocated regions in the Hi-C data with previously published MCF-10A and MCF-7 spectral karyotyping (SKY) and multiplex fluorescence in situ hybridization (M-FISH) data [49, 50], we observed that the majority of the translocated regions identified by SKY/M-FISH were identified by Hi-C (Figures S3 and S4 in Additional file 1)
Summary
Higher-order chromatin structure is often perturbed in cancer and other pathological states. 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. Three-dimensional genome organization is important for regulation of gene expression by bringing together distant promoter, enhancer and other cis-regulatory regions [1,2,3]. The higher-order folding of chromatin within the nucleus involves hierarchical structures spanning different length scales [10]. Increasing evidence highlights the importance of chromosome and gene positioning during breast cancer initiation [15,16,17]. Recent evidence demonstrates the influence of Barutcu et al Genome Biology (2015) 16:214 physical spatial proximity in the nucleus on recurrent translocations [18,19,20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
