title: Estrogen induces global reorganization of chromatin structure in human breast cancer cells.
abstract: In the cell nucleus, each chromosome is confined to a chromosome territory. This spatial organization of chromosomes plays a crucial role in gene regulation and genome stability. An additional level of organization has been discovered at the chromosome scale: the spatial segregation into open and closed chromatins to form two genome-wide compartments. Although considerable progress has been made in our knowledge of chromatin organization, a fundamental issue remains the understanding of its dynamics, especially in cancer. To address this issue, we performed genome-wide mapping of chromatin interactions (Hi-C) over the time after estrogen stimulation of breast cancer cells. To biologically interpret these interactions, we integrated with estrogen receptor α (ERα) binding events, gene expression and epigenetic marks. We show that gene-rich chromosomes as well as areas of open and highly transcribed chromatins are rearranged to greater spatial proximity, thus enabling genes to share transcriptional machinery and regulatory elements. At a smaller scale, differentially interacting loci are enriched for cancer proliferation and estrogen-related genes. Moreover, these loci are correlated with higher ERα binding events and gene expression. Taken together these results reveal the role of a hormone--estrogen--on genome organization, and its effect on gene regulation in cancer.
authors.affiliation: Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana School of Medicine, Indiana University, Indianapolis, IN, 46202, United States of America.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Mourad
authors.affiliation: Departments of Molecular Medicine/Institute of Biotechnology, University of Texas Health Science Center, San Antonio, TX, 78245, United States of America.
authors.forename: Pei-Yin
authors.initials: PY
authors.lastname: Hsu
authors.affiliation: Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana School of Medicine, Indiana University, Indianapolis, IN, 46202, United States of America.
authors.forename: Liran
authors.initials: L
authors.lastname: Juan
authors.affiliation: Department of Biostatistics, Center for Computational Biology and Bioinformatics, Indiana School of Medicine, Indiana University, Indianapolis, IN, 46202, United States of America.
authors.forename: Changyu
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana School of Medicine, Indiana University, Indianapolis, IN, 46202, United States of America.
authors.forename: Prasad
authors.initials: P
authors.lastname: Koneru
authors.affiliation: Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana School of Medicine, Indiana University, Indianapolis, IN, 46202, United States of America.
authors.forename: Hai
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana School of Medicine, Indiana University, Indianapolis, IN, 46202, United States of America.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Ovarian Cancer Epigenomics, Indiana University, Bloomington, IN, 47405, United States of America.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Nephew
authors.affiliation: Departments of Molecular Medicine/Institute of Biotechnology, University of Texas Health Science Center, San Antonio, TX, 78245, United States of America.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Huang
authors.affiliation: Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana School of Medicine, Indiana University, Indianapolis, IN, 46202, United States of America.
authors.forename: Lang
authors.initials: L
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002877:Chromosomes, Human / Q000737:chemistry / Q000235:genetics; D044127:Epigenesis, Genetic; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056426:Genetic Loci; D006801:Humans; D061986:MCF-7 Cells
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol