Dataset Information

The genomic landscape of estrogen receptor ? binding sites in mouse mammary gland.

ABSTRACT: Estrogen receptor ? (ER?) is the major driving transcription factor in the mammary gland development as well as breast cancer initiation and progression. However, the genomic landscape of ER? binding sites in the normal mouse mammary gland has not been completely elucidated. Here, we mapped genome-wide ER? 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 ER? 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 ER? ChIP-seq data, we uncovered a novel ER? targetome in mouse mammary epithelial cells. Taken together, our study has identified the genomic landscape of ER? 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.

SUBMITTER: Palaniappan M

PROVIDER: S-EPMC6692022 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The genomic landscape of estrogen receptor α binding sites in mouse mammary gland.

Palaniappan Murugesan M Nguyen Loc L Grimm Sandra L SL Xi Yuanxin Y Xia Zheng Z Li Wei W Coarfa Cristian C

PloS one 20190813 8

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 bi ...[more]

PMID: 31408468

Similar Datasets

Project description:Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing strategy, we mapped estrogen receptor alpha (ERalpha) binding sites in MCF-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94% are projected to be bona fide ERalpha binding regions. Only 5% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations (>5 kb from 5' and 3' ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71% harbored putative full estrogen response elements (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences. Genes in the vicinity of ERalpha binding sites were enriched for regulation by estradiol in MCF-7 cells, and their expression profiles in patient samples segregate ERalpha-positive from ERalpha-negative breast tumors. The expression dynamics of the genes adjacent to ERalpha binding sites suggest a direct induction of gene expression through binding to ERE-like sequences, whereas transcriptional repression by ERalpha appears to be through indirect mechanisms. Our analysis also indicates a number of candidate transcription factor binding sites adjacent to occupied EREs at frequencies much greater than by chance, including the previously reported FOXA1 sites, and demonstrate the potential involvement of one such putative adjacent factor, Sp1, in the global regulation of ERalpha target genes. Unexpectedly, we found that only 22%-24% of the bona fide human ERalpha binding sites were overlapping conserved regions in whole genome vertebrate alignments, which suggest limited conservation of functional binding sites. Taken together, this genome-scale analysis suggests complex but definable rules governing ERalpha binding and gene regulation.

Dataset Information

The genomic landscape of estrogen receptor ? binding sites in mouse mammary gland.

Publications

The genomic landscape of estrogen receptor α binding sites in mouse mammary gland.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets