@article{Caizzi2014,
abstract = {Estrogen receptor-$\alpha$ (ER$\alpha$) has central role in hormone-dependent breast cancer and its ligand-induced functions have been extensively characterized. However, evidence exists that ER$\alpha$ has functions that are independent of ligands. In the present work, we investigated the binding of ER$\alpha$ to chromatin in the absence of ligands and its functions on gene regulation. We demonstrated that in MCF7 breast cancer cells unliganded ER$\alpha$ binds to more than 4,000 chromatin sites. Unexpectedly, although almost entirely comprised in the larger group of estrogen-induced binding sites, we found that unliganded-ER$\alpha$ binding is specifically linked to genes with developmental functions, compared with estrogen-induced binding. Moreover, we found that siRNA-mediated down-regulation of ER$\alpha$ in absence of estrogen is accompanied by changes in the expression levels of hundreds of coding and noncoding RNAs. Down-regulated mRNAs showed enrichment in genes related to epithelial cell growth and development. Stable ER$\alpha$ down-regulation using shRNA, which caused cell growth arrest, was accompanied by increased H3K27me3 at ER$\alpha$ binding sites. Finally, we found that FOXA1 and AP2$\gamma$ binding to several sites is decreased upon ER$\alpha$ silencing, suggesting that unliganded ER$\alpha$ participates, together with other factors, in the maintenance of the luminal-specific cistrome in breast cancer cells.},
author = {Caizzi, Livia and Ferrero, Giulio and Cutrupi, Santina and Cordero, Francesca and Ballar\'{e}, Cecilia and Miano, Valentina and Reineri, Stefania and Ricci, Laura and Friard, Olivier and Testori, Alessandro and Cor\`{a}, Davide and Caselle, Michele and {Di Croce}, Luciano and {De Bortoli}, Michele},
doi = {10.1073/pnas.1315445111},
file = {:home/giulio/.local/share/data/Mendeley Ltd./Mendeley Desktop/Downloaded/Caizzi et al. - 2014 - Genome-wide activity of unliganded estrogen receptor-$\alpha$ in breast cancer cells.pdf:pdf},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
keywords = {Binding Sites,Breast Neoplasms,Breast Neoplasms: genetics,Breast Neoplasms: pathology,Cell Proliferation,Chromatin Immunoprecipitation,Estrogen Receptor alpha,Estrogen Receptor alpha: metabolism,Female,Gene Ontology,Genome, Human,Genome, Human: genetics,Humans,Ligands,MCF-7 Cells,Polymerase Chain Reaction,RNA, Small Interfering,RNA, Small Interfering: metabolism},
month = apr,
number = {13},
pages = {4892--7},
pmid = {24639548},
title = {{Genome-wide activity of unliganded estrogen receptor-$\alpha$ in breast cancer cells.}},
url = {http://www.pnas.org/content/111/13/4892.short},
volume = {111},
year = {2014}
}