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

PLoS ONE ◽  
2019 ◽  
Vol 14 (8) ◽  
pp. e0220311 ◽  
Author(s):  
Murugesan Palaniappan ◽  
Loc Nguyen ◽  
Sandra L. Grimm ◽  
Yuanxin Xi ◽  
Zheng Xia ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Binding Sites ◽  
Estrogen Receptor Α ◽  
Mouse Mammary Gland ◽  
Genomic Landscape

scholarly journals AKT Alters Genome-Wide Estrogen Receptor α Binding and Impacts Estrogen Signaling in Breast Cancer

2008 ◽  
Vol 28 (24) ◽  
pp. 7487-7503 ◽  
Author(s):  
Poornima Bhat-Nakshatri ◽  
Guohua Wang ◽  
Hitesh Appaiah ◽  
Nikhil Luktuke ◽  
Jason S. Carroll ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Binding Sites ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Primary Tumors ◽  
Genome Wide ◽  
Extracellular Signal

ABSTRACT Estrogen regulates several biological processes through estrogen receptor α (ERα) and ERβ. ERα-estrogen signaling is additionally controlled by extracellular signal activated kinases such as AKT. In this study, we analyzed the effect of AKT on genome-wide ERα binding in MCF-7 breast cancer cells. Parental and AKT-overexpressing cells displayed 4,349 and 4,359 ERα binding sites, respectively, with ∼60% overlap. In both cell types, ∼40% of estrogen-regulated genes associate with ERα binding sites; a similar percentage of estrogen-regulated genes are differentially expressed in two cell types. Based on pathway analysis, these differentially estrogen-regulated genes are linked to transforming growth factor β (TGF-β), NF-κB, and E2F pathways. Consistent with this, the two cell types responded differently to TGF-β treatment: parental cells, but not AKT-overexpressing cells, required estrogen to overcome growth inhibition. Combining the ERα DNA-binding pattern with gene expression data from primary tumors revealed specific effects of AKT on ERα binding and estrogen-regulated expression of genes that define prognostic subgroups and tamoxifen sensitivity of ERα-positive breast cancer. These results suggest a unique role of AKT in modulating estrogen signaling in ERα-positive breast cancers and highlights how extracellular signal activated kinases can change the landscape of transcription factor binding to the genome.

scholarly journals The Phosphorylated Estrogen Receptor α (ER) Cistrome Identifies a Subset of Active Enhancers Enriched for Direct ER-DNA Binding and the Transcription Factor GRHL2

2018 ◽  
Vol 39 (3) ◽  
Author(s):  
Kyle T. Helzer ◽  
Mary Szatkowski Ozers ◽  
Mark B. Meyer ◽  
Nancy A. Benkusky ◽  
Natalia Solodin ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Transcription Factor ◽  
Dna Binding ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Binding Sites ◽  
Protein Function ◽  
Estrogen Receptor Α ◽  
Binding Activity

ABSTRACT Posttranslational modifications are key regulators of protein function, providing cues that can alter protein interactions and cellular location. Phosphorylation of estrogen receptor α (ER) at serine 118 (pS118-ER) occurs in response to multiple stimuli and is involved in modulating ER-dependent gene transcription. While the cistrome of ER is well established, surprisingly little is understood about how phosphorylation impacts ER-DNA binding activity. To define the pS118-ER cistrome, chromatin immunoprecipitation sequencing was performed on pS118-ER and ER in MCF-7 cells treated with estrogen. pS118-ER occupied a subset of ER binding sites which were associated with an active enhancer mark, acetylated H3K27. Unlike ER, pS118-ER sites were enriched in GRHL2 DNA binding motifs, and estrogen treatment increased GRHL2 recruitment to sites occupied by pS118-ER. Additionally, pS118-ER occupancy sites showed greater enrichment of full-length estrogen response elements relative to ER sites. In an in vitro DNA binding array of genomic binding sites, pS118-ER was more commonly associated with direct DNA binding events than indirect binding events. These results indicate that phosphorylation of ER at serine 118 promotes direct DNA binding at active enhancers and is a distinguishing mark for associated transcription factor complexes on chromatin.

Induction of Estrogen Receptor α Expression with Decoy Oligonucleotide Targeted to NFATc1 Binding Sites in Osteoblasts

2007 ◽  
Vol 71 (6) ◽  
pp. 1457-1462 ◽  
Author(s):  
Letizia Penolazzi ◽  
Margherita Zennaro ◽  
Elisabetta Lambertini ◽  
Elisa Tavanti ◽  
Elena Torreggiani ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Binding Sites ◽  
Estrogen Receptor Α ◽  
Decoy Oligonucleotide

Involvement of estrogen receptors α and β in the regulation of cervical permeability

2000 ◽  
Vol 278 (4) ◽  
pp. C689-C696 ◽  
Author(s):  
George I. Gorodeski ◽  
Dipika Pal
Keyword(s):  
Estrogen Receptor ◽  
Binding Sites ◽  
Estrogen Receptor Α ◽  
Binding Activity ◽  
Scatchard Analysis ◽  
Single Class ◽  
Estrogen Receptor Modulators ◽  
Transcription Inhibitor ◽  
Estrogen Binding ◽  
In Cells

Estrogen increases the permeability of cultured human cervical epithelia (Gorodeski, GI. Am J Physiol Cell Physiol 275: C888–C899, 1998), and the effect is blocked by the estrogen receptor modulators ICI-182780 and tamoxifen. The objective of the study was to determine involvement of estrogen receptor(s) in mediating the effects on permeability. In cultured human cervical epithelial cells estradiol binds to high-affinity, low-capacity sites, in a specific and saturable manner. Scatchard analysis revealed a single class of binding sites with a dissociation constant of 1.3 nM and binding activity of ∼0.5 pmol/mg DNA. Estradiol increased the density of estrogen-binding sites in a time- and dose-related manner (half time ≈ 4 h, and EC50≈ 1 nM). RT-PCR assays revealed the expression of mRNA for the estrogen receptor α (αER) and estrogen receptor β (βER). Removal of estrogen from the culture medium decreased and treatment with estrogen increased the expression of αER and βER mRNA. In cells not treated with estrogen, ICI-182780 and tamoxifen increased βER mRNA. In cells treated with estrogen, neither ICI-182780 nor tamoxifen had modulated significantly the increase in αER or βER mRNA. The transcription inhibitor actinomycin D blocked the estrogen-induced increase in permeability, and it abrogated the estradiol-induced increase in estrogen binding sites. These results suggest that the estrogen-dependent increase in cervical permeability is mediated by an αER-dependent increase in transcription.

scholarly journals Quantitative Analysis of Estrogen Receptor Proteins in Rat Mammary Gland*

Endocrinology ◽  
2001 ◽  
Vol 142 (7) ◽  
pp. 3177-3186 ◽  
Author(s):  
Shigehira Saji ◽  
Hideki Sakaguchi ◽  
Sandra Andersson ◽  
Margaret Warner ◽  
Jan-Åke Gustafsson
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Total Protein ◽  
Messenger Rna ◽  
Estrogen Receptor Α ◽  
Lactation Period ◽  
Binding Assays ◽  
Western Blots ◽  
Mean Values ◽  
Rat Mammary Gland

Abstract Estrogen receptor α and β proteins (ERα and ERβ) at various stages of development of the rat mammary gland were quantified by Western blotting. ERα and ERβ recombinant proteins were used as standards, and their molar concentrations were measured by ligand binding assays. In 3-week-old pregnant, lactating, and postlactating rats the ERα content ranged from 0.30–1.55 fmol/μg total protein (mean values). The ERβ content of the same samples ranged between 1.06–7.50 fmol/μg total protein. At every developmental stage, the ERβ content of the mammary gland was higher than that of ERα. When receptor levels were normalized against β-actin, it was evident that ER expression changed during development, with maximum expression of both receptors during the lactation period. With an antibody raised against the 18-amino acid insert of the ERβ variant, originally called ERβ2 but named ERβins in this paper, Western blots revealed that ERβins protein was up-regulated during the lactation period. RT-PCR showed that the levels of messenger RNA of ERβins paralleled those of the protein. Double immunohistochemical staining with anti-ERα and anti-ERβins antibodies revealed that ERβins protein colocalized with ERα in 70–80% of the ERα-expressing epithelial cells during lactation and with 30% of these cells during pregnancy. These observations indicate that expression of ERβins is regulated not only quantitatively, but also with regard to its cellular distribution. As ERβins acts as the dominant repressor of ERα, we suggest that its coexpression with ERα quenches ERα function and may be one of the factors that contribute to the previously described insensitivity of the mammary gland to estrogens during lactation.

scholarly journals Genome-Wide Identification of Estrogen Receptor α-Binding Sites in Mouse Liver

2008 ◽  
Vol 22 (1) ◽  
pp. 10-22 ◽  
Author(s):  
Hui Gao ◽  
Susann Fält ◽  
Albin Sandelin ◽  
Jan-Åke Gustafsson ◽  
Karin Dahlman-Wright
Keyword(s):  
Estrogen Receptor ◽  
Binding Sites ◽  
Mouse Liver ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Transcription Start ◽  
Expression Levels ◽  
Transcription Start Sites ◽  
Genome Wide ◽  
Binding Regions

Abstract We report the genome-wide identification of estrogen receptor α (ERα)-binding regions in mouse liver using a combination of chromatin immunoprecipitation and tiled microarrays that cover all nonrepetitive sequences in the mouse genome. This analysis identified 5568 ERα-binding regions. In agreement with what has previously been reported for human cell lines, many ERα-binding regions are located far away from transcription start sites; approximately 40% of ERα-binding regions are located within 10 kb of annotated transcription start sites. Almost 50% of ERα-binding regions overlap genes. The majority of ERα-binding regions lie in regions that are evolutionarily conserved between human and mouse. Motif-finding algorithms identified the estrogen response element, and variants thereof, together with binding sites for activator protein 1, basic-helix-loop-helix proteins, ETS proteins, and Forkhead proteins as the most common motifs present in identified ERα-binding regions. To correlate ERα binding to the promoter of specific genes, with changes in expression levels of the corresponding mRNAs, expression levels of selected mRNAs were assayed in livers 2, 4, and 6 h after treatment with ERα-selective agonist propyl pyrazole triol. Five of these eight selected genes, Shp, Stat3, Pdgds, Pck1, and Pdk4, all responded to propyl pyrazole triol after 4 h treatment. These results extend our previous studies using gene expression profiling to characterize estrogen signaling in mouse liver, by characterizing the first step in this signaling cascade, the binding of ERα to DNA in intact chromatin.

scholarly journals Unliganded estrogen receptor-α activates transcription of the mammary gland Na+/I− symporter gene

2006 ◽  
Vol 345 (4) ◽  
pp. 1487-1496 ◽  
Author(s):  
Hani Alotaibi ◽  
Elif Çankaya Yaman ◽  
Ediz Demirpençe ◽  
Uygar H. Tazebay
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Estrogen Receptor Α

Neonatal Experiences Differentially Influence Mammary Gland Morphology, Estrogen Receptor α Protein Levels, and Carcinogenesis in BALB/c Mice

2010 ◽  
Vol 3 (11) ◽  
pp. 1398-1408 ◽  
Author(s):  
Allison L. Boyd ◽  
Ayesha Salleh ◽  
Brent Humber ◽  
Janet Yee ◽  
Ladislav Tomes ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Estrogen Receptor Α ◽  
Protein Levels ◽  
Mammary Gland Morphology

Estrogen receptor-negative epithelial cells in mouse mammary gland development and growth

1998 ◽  
Vol 62 (5) ◽  
pp. 221-226 ◽  
Author(s):  
Nikolajs Zeps ◽  
Jacqueline M. Bentel ◽  
John M. Papadimitriou ◽  
Mario F. D'Antuono ◽  
Hugh J.S. Dawkins
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Gland Development ◽  
Mouse Mammary Gland ◽  
Gland Development ◽  
Estrogen Receptor Negative
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