title: Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.
authors.forename: A Rasim
authors.initials: AR
authors.lastname: Barutcu
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Lajoie
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.
authors.forename: Rachel P
authors.initials: RP
authors.lastname: McCord
authors.affiliation: Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Coralee E
authors.initials: CE
authors.lastname: Tye
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.|Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Deli
authors.initials: D
authors.lastname: Hong
authors.affiliation: Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Terri L
authors.initials: TL
authors.lastname: Messier
authors.affiliation: Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Gillian
authors.initials: G
authors.lastname: Browne
authors.affiliation: Department of Biochemistry & Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.affiliation: Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.affiliation: Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.|Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.
authors.forename: Job
authors.initials: J
authors.lastname: Dekker
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Imbalzano
authors.affiliation: Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, 05405, USA. gary.stein@uvm.edu.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis; D002843:Chromatin / Q000235:genetics*; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D016615:Telomere / Q000235:genetics*
chemical_list: D002843:Chromatin