TY - JOUR
T1 - Estrogen induces global reorganization of chromatin structure In human breast cancer cells
AU - Mourad, Raphaël
AU - Hsu, Pei Yin
AU - Juan, Liran
AU - Shen, Changyu
AU - Koneru, Prasad
AU - Lin, Hai
AU - Liu, Yunlong
AU - Nephew, Kenneth
AU - Huang, Tim H.
AU - Li, Lang
N1 - Publisher Copyright:
© 2014 Mourad et al.
PY - 2014/12/3
Y1 - 2014/12/3
N2 - 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 ERa 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.
AB - 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 ERa 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.
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U2 - 10.1371/journal.pone.0113354
DO - 10.1371/journal.pone.0113354
M3 - Article
C2 - 25470140
AN - SCOPUS:84915756658
SN - 1932-6203
VL - 9
JO - PLoS One
JF - PLoS One
IS - 12
M1 - e113354
ER -