Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells
AuthorsBarutcu, Ahmet Rasim
Lajoie, Bryan R.
McCord, Rachel Patton
Tye, Coralee E.
Messier, Terri L.
van Wijnen, Andre J.
Lian, Jane B.
Stein, Janet L.
Imbalzano, Anthony N.
Stein, Gary S.
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Program in Systems Biology
Department of Cell and Developmental Biology
Document TypeJournal Article
MetadataShow full item record
AbstractBACKGROUND: 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.
SourceGenome Biol. 2015 Sep 28;16(1):214. doi: 10.1186/s13059-015-0768-0. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/49956
© 2015 Barutcu et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.