Mourad, RaphaelHsu, Pei-YinJuran, LiranShen, ChangyuKoneru, PrasadLin, HaiLiu, YunlongNephew, KennethHuang, Tim H.Li, Lang2016-06-152016-06-152014-12-03Mourad, R., Hsu, P.-Y., Juan, L., Shen, C., Koneru, P., Lin, H., … Li, L. (2014). Estrogen Induces Global Reorganization of Chromatin Structure in Human Breast Cancer Cells. PLoS ONE, 9(12), e113354. http://doi.org/10.1371/journal.pone.0113354https://hdl.handle.net/1805/9985In 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.en-USPublisher PolicyBinding SitesBreast NeoplasmsChromatin Assembly and DisassemblyEstradiolEstrogenGene Expression Regulation, NeoplasticGenetic LociArticle