Estrogen induces global reorganization of chromatin structure in human breast cancer cells.
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 cl...
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doaj-55b25c94bc6042e18e4a62c69ba3762d2021-03-03T20:11:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11335410.1371/journal.pone.0113354Estrogen induces global reorganization of chromatin structure in human breast cancer cells.Raphaël MouradPei-Yin HsuLiran JuanChangyu ShenPrasad KoneruHai LinYunlong LiuKenneth NephewTim H HuangLang LiIn 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.https://doi.org/10.1371/journal.pone.0113354 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Raphaël Mourad Pei-Yin Hsu Liran Juan Changyu Shen Prasad Koneru Hai Lin Yunlong Liu Kenneth Nephew Tim H Huang Lang Li |
spellingShingle |
Raphaël Mourad Pei-Yin Hsu Liran Juan Changyu Shen Prasad Koneru Hai Lin Yunlong Liu Kenneth Nephew Tim H Huang Lang Li Estrogen induces global reorganization of chromatin structure in human breast cancer cells. PLoS ONE |
author_facet |
Raphaël Mourad Pei-Yin Hsu Liran Juan Changyu Shen Prasad Koneru Hai Lin Yunlong Liu Kenneth Nephew Tim H Huang Lang Li |
author_sort |
Raphaël Mourad |
title |
Estrogen induces global reorganization of chromatin structure in human breast cancer cells. |
title_short |
Estrogen induces global reorganization of chromatin structure in human breast cancer cells. |
title_full |
Estrogen induces global reorganization of chromatin structure in human breast cancer cells. |
title_fullStr |
Estrogen induces global reorganization of chromatin structure in human breast cancer cells. |
title_full_unstemmed |
Estrogen induces global reorganization of chromatin structure in human breast cancer cells. |
title_sort |
estrogen induces global reorganization of chromatin structure in human breast cancer cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pone.0113354 |
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