The genomic landscape of estrogen receptor α binding sites in mouse mammary gland.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
12
2018
accepted:
12
07
2019
entrez:
14
8
2019
pubmed:
14
8
2019
medline:
29
2
2020
Statut:
epublish
Résumé
Estrogen receptor α (ERα) is the major driving transcription factor in the mammary gland development as well as breast cancer initiation and progression. However, the genomic landscape of ERα binding sites in the normal mouse mammary gland has not been completely elucidated. Here, we mapped genome-wide ERα binding events by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in the mouse mammary gland in response to estradiol. We identified 6237 high confidence ERα binding sites in two biological replicates and showed that many of these were located at distal enhancer regions. Furthermore, we discovered 3686 unique genes in the mouse genome that recruit ER in response to estradiol. Interrogation of ER-DNA binding sites in ER-positive luminal epithelial cells showed that the ERE, PAX2, SF1, and AP1 motifs were highly enriched at distal enhancer regions. In addition, comprehensive transcriptome analysis by RNA-seq revealed that 493 genes are differentially regulated by acute treatment with estradiol in the mouse mammary gland in vivo. Through integration of RNA-seq and ERα ChIP-seq data, we uncovered a novel ERα targetome in mouse mammary epithelial cells. Taken together, our study has identified the genomic landscape of ERα binding events in mouse mammary epithelial cells. Furthermore, our study also highlights the cis-regulatory elements and cofactors that are involved in estrogen signaling and may contribute to ductal elongation in the normal mouse mammary gland.
Identifiants
pubmed: 31408468
doi: 10.1371/journal.pone.0220311
pii: PONE-D-18-36596
pmc: PMC6692022
doi:
Substances chimiques
Estrogen Receptor alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0220311Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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