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Mapping ERβ Genomic Binding Sites Reveals Unique Genomic Features and Identifies EBF1 as an ERβ Interactor

Considerable effort by numerous laboratories has resulted in an improved understanding of estrogen and SERM action mediated by the two estrogen receptors, ERα and ERβ. However, many of the targets for ERβ in cell physiology remain elusive. Here, the C4-12/Flag.ERβ cell line which stably expressed Fl...

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Autores principales: Le, Thien P., Sun, Miao, Luo, Xin, Kraus, W. Lee, Greene, Geoffrey L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738513/
https://www.ncbi.nlm.nih.gov/pubmed/23951143
http://dx.doi.org/10.1371/journal.pone.0071355
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author Le, Thien P.
Sun, Miao
Luo, Xin
Kraus, W. Lee
Greene, Geoffrey L.
author_facet Le, Thien P.
Sun, Miao
Luo, Xin
Kraus, W. Lee
Greene, Geoffrey L.
author_sort Le, Thien P.
collection PubMed
description Considerable effort by numerous laboratories has resulted in an improved understanding of estrogen and SERM action mediated by the two estrogen receptors, ERα and ERβ. However, many of the targets for ERβ in cell physiology remain elusive. Here, the C4-12/Flag.ERβ cell line which stably expressed Flag.ERβ is used to study ERβ genomic functions without ERα interference. Mapping ERβ binding sites in these cells reveals ERβ unique distribution and motif enrichment patterns. Accompanying our mapping results, nascent RNA profiling is performed on cells at the same treatment time. The combined results allow the identification of ERβ target genes. Gene ontology analysis reveals that ERβ targets are enriched in differentiation, development and apoptosis. Concurrently, E2 treatment suppresses proliferation in these cells. Within ERβ binding sites, while the most prevalent binding motif is the canonical ERE, motifs of known ER interactors are also enriched in ERβ binding sites. Moreover, among enriched binding motifs are those of GFI, REST and EBF1, which are unique to ERβ binding sites in these cells. Further characterization confirms the association between EBF1 and the estrogen receptors, which favors the N-terminal region of the receptor. Furthermore, EBF1 negatively regulates ERs at the protein level. In summary, by studying ERβ genomic functions in our cell model, we confirm the anti-proliferative role of ERβ and discover the novel cross talk of ERβ with EBF1 which has various implications in normal physiology.
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spelling pubmed-37385132013-08-15 Mapping ERβ Genomic Binding Sites Reveals Unique Genomic Features and Identifies EBF1 as an ERβ Interactor Le, Thien P. Sun, Miao Luo, Xin Kraus, W. Lee Greene, Geoffrey L. PLoS One Research Article Considerable effort by numerous laboratories has resulted in an improved understanding of estrogen and SERM action mediated by the two estrogen receptors, ERα and ERβ. However, many of the targets for ERβ in cell physiology remain elusive. Here, the C4-12/Flag.ERβ cell line which stably expressed Flag.ERβ is used to study ERβ genomic functions without ERα interference. Mapping ERβ binding sites in these cells reveals ERβ unique distribution and motif enrichment patterns. Accompanying our mapping results, nascent RNA profiling is performed on cells at the same treatment time. The combined results allow the identification of ERβ target genes. Gene ontology analysis reveals that ERβ targets are enriched in differentiation, development and apoptosis. Concurrently, E2 treatment suppresses proliferation in these cells. Within ERβ binding sites, while the most prevalent binding motif is the canonical ERE, motifs of known ER interactors are also enriched in ERβ binding sites. Moreover, among enriched binding motifs are those of GFI, REST and EBF1, which are unique to ERβ binding sites in these cells. Further characterization confirms the association between EBF1 and the estrogen receptors, which favors the N-terminal region of the receptor. Furthermore, EBF1 negatively regulates ERs at the protein level. In summary, by studying ERβ genomic functions in our cell model, we confirm the anti-proliferative role of ERβ and discover the novel cross talk of ERβ with EBF1 which has various implications in normal physiology. Public Library of Science 2013-08-08 /pmc/articles/PMC3738513/ /pubmed/23951143 http://dx.doi.org/10.1371/journal.pone.0071355 Text en © 2013 Le et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Le, Thien P.
Sun, Miao
Luo, Xin
Kraus, W. Lee
Greene, Geoffrey L.
Mapping ERβ Genomic Binding Sites Reveals Unique Genomic Features and Identifies EBF1 as an ERβ Interactor
title Mapping ERβ Genomic Binding Sites Reveals Unique Genomic Features and Identifies EBF1 as an ERβ Interactor
title_full Mapping ERβ Genomic Binding Sites Reveals Unique Genomic Features and Identifies EBF1 as an ERβ Interactor
title_fullStr Mapping ERβ Genomic Binding Sites Reveals Unique Genomic Features and Identifies EBF1 as an ERβ Interactor
title_full_unstemmed Mapping ERβ Genomic Binding Sites Reveals Unique Genomic Features and Identifies EBF1 as an ERβ Interactor
title_short Mapping ERβ Genomic Binding Sites Reveals Unique Genomic Features and Identifies EBF1 as an ERβ Interactor
title_sort mapping erβ genomic binding sites reveals unique genomic features and identifies ebf1 as an erβ interactor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738513/
https://www.ncbi.nlm.nih.gov/pubmed/23951143
http://dx.doi.org/10.1371/journal.pone.0071355
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