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GSE40663
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Progesterone (P4) signaling through its nuclear transcription factor, the progesterone receptor (PR), is essential for normal uterine function. Although deregulation of PR mediated signaling is known to underscore uterine dysfunction and a number of endometrial pathologies, the early molecular mechanisms of this deregulation are unclear. To address this issue, we have defined the genome-wide PR and GATA2 cistrome in the murine uterus using chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq). In uteri of ovariectomized mice, we identified 6367 PR binding sites in the absence of P4 ligand; however, this number increased at nearly three fold (18,432) following acute P4 exposure. Sequence analysis revealed that approximately 73% of these binding sites contain a progesterone response element (PRE) or a half-site motif recognized by the PR. Many previously identified P4 target genes known to regulate uterine function were found to contain PR binding sites, confirming the validity of our methodology. In addition we identified 46,183 GATA2 binding sites in P4 treatment conditions with 7,954 binding sites overlapping that of the PR.
Publication Title
Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ovarian estrogen (E2) and progesterone (P4) are indispensable for embryo-implantation and endometrial stromal decidualization; however, the molecular mechanisms that underpin these reproductive processes are unclear. Steroid receptor coregulator-2 (SRC-2) belongs to the multifunctional SRC/p160 family which also includes SRC-1 and SRC-3. Sharing strong sequence homology, all three SRCs exert diverse regulatory effects by modulating the transcriptional potency of nuclear receptor family members, including the estrogen and progesterone receptor (ER and PR respectively). Importantly, absence of SRC-2 in PR positive cells in the epithelial, stromal, and myometrial compartments of the murine uterus results in a striking infertility defect. This reproductive phenotype highlights a key role for SRC-2 in uterine function which is not shared with other coregulators. Intriguingly, abrogation of uterine SRC-2 does not block embryo apposition or attachment to the apical surface of luminal epithelial cells of the endometrium but rather prevents P4-dependent local decidualization of the sub-epithelial stroma. Remarkably, epithelial-specific ablation of SRC-2 in the murine uterus does not compromise endometrial functionality, again underscoring the unique importance of stromal derived SRC-2 in uterine function. The stromal decidualization defect resulting from SRC-2 ablation is reflected at the molecular level by a marked attenuation in P4 responsive target genes known to be critical for P4 dependent decidualization (i.e. ERBB receptor feedback inhibitor 1, Follistatin and Fkbp5). Conversely, the induction of E2 or P4 target genes involved in embryo implantation (i.e. leukemia inhibitory factor (LIF) and Indian hedgehog (Ihh) respectively) is not affected by SRC-2s absence. As with mouse studies, decidualization of primary human stromal cells (HESCs) in culture is blocked by SRC-2 knockdown; however, HESC decidualization is unaffected by knockdown of SRC-1 or SRC-3. As a consequence of SRC-2 knockdown, molecular studies disclose a striking decrease in the induction of a subset of P4 target genes (i.e. WNT4 and FKBP5) which are essential for the stromal-epithelioid transformation step, the cellular hallmark of endometrial decidualization. Collectively, these studies not only showcase the evolutionary importance of SRC-2 in endometrial biology but also suggest that deregulation of this coregulator may underpin a spectrum of hormone-dependent uterine pathologies such as endometriosis and endometrial cancer.
Publication Title
A murine uterine transcriptome, responsive to steroid receptor coactivator-2, reveals transcription factor 23 as essential for decidualization of human endometrial stromal cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
Illumina HiSeq 2500
Description
RNA-sequencing of mRNA isolated from in vitro decidualizaing human endometrial stromal cells with or without siRNA-mediated knockdown of steroid receptor coactivator-2/nuclear receptor coactivator 2 (SRC-2/NCOA2) Overall design: Primary human endometrial stromal cells isolated from 3 healthy volunteers. Transfected with nontargeting or SRC-2/NCOA2 siRNA. Treated with estradiol, medroxyprogesterone acetate, and cAMP (EPC) for 0 or 3 days
Publication Title
Retinoid signaling controlled by SRC-2 in decidualization revealed by transcriptomics
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-sequencing of mRNA isolated from in vitro decidualizaing human endometrial stromal cells with or without siRNA-mediated knockdown of PLZF Overall design: Primary human endometrial stromal cells isolated from 3 healthy volunteers. Transfected with nontargeting or PLZF siRNA. Treated with estradiol, medroxyprogesterone acetate, and cAMP (EPC) for 0 or 3 days
Publication Title
Human endometrial stromal cell decidualization requires transcriptional reprogramming by PLZF.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gata2 dependent genes in mouse uteri were identified by the conditional ablation of Gata2 using the (PR-cre) mouse upon acute progesterone administration.
Publication Title
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration.
Publication Title
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Two subtypes of the estrogen receptor, ERalpha and ERbeta, mediate the actions of estrogens, and the majority of human breast tumors contain both ERalpha and ERbeta. To examine the possible interactions and modulatory effects of ERbeta on ERalpha activity, we have used adenoviral gene delivery to produce human breast cancer (MCF-7) cells expressing ERbeta, along with their endogenous ERalpha. We have examined the effects of ER expression on genome-wide gene expression by Affymetrix GeneChip microarrays. We find that ERbeta modulated estrogen gene expression on nearly 24% of E2-stimulated genes but only 8% of E2-inhibited genes. We find that ERbeta modulation is gene-specific, enhancing or counteracting ERalpha regulation for distinct subsets of estrogen target genes. Introduction of ERbeta into ERalpha-containing cells induced up/down-regulation of many estrogen target in the absence of any added ligand. In addition, ERbeta presence elicited the expression of a unique set of genes that were not regulated by ERalpha alone. ERbeta modulated the expression of genes in many functional categories, but the greatest numbers were associated with transcription factor and signal transduction pathways. Regulation of multiple components in the TGF beta, SDF1, and semaphorin pathways, may contribute to the suppression of proliferation observed with ERbeta both in the presence and absence of estrogen. Hence, ERbeta modulates ERalpha gene regulation in diverse ways that may contribute to its growth-inhibiting beneficial effects in breast cancer
Publication Title
Impact of estrogen receptor beta on gene networks regulated by estrogen receptor alpha in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 104 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We used microarrays to detail the global transcriptional response mediated by ERalpha or ERbeta to the phytoestrogen genistein in the MCF-7 human breast cancer cell model.
Publication Title
Estrogen Receptors alpha and beta as determinants of gene expression: influence of ligand, dose, and chromatin binding.
Sample Metadata Fields
No sample metadata fields
View Samples