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Relaxin Attenuates the Genomic Actions and Biological Effects of Estrogens in the Myometrium by Reducing Estrogen Receptor Alpha Phosphorylation [ChIP-seq]

ABSTRACT: In this study we examine the extent and nature of functional interactions between the E2 and Rln signaling pathways in the myometrium. In addition, we delineate the mechanisms underlying functional interplay between the E2/ERα and Rln/RXFP1 signaling pathways at the molecular and physiological levels in myometrial tissue and cells during quiescence and contractility.

ORGANISM(S): Mus musculus

PROVIDER: GSE244841 | GEO | 2024/05/10

REPOSITORIES: GEO

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Relaxin Attenuates the Genomic Actions and Biological Effects of Estrogens in the Myometrium by Reducing Estrogen Receptor Alpha Phosphorylation [RNA-seq]

Project description:In this study we examine the extent and nature of functional interactions between the E2 and Rln signaling pathways in the myometrium. In addition, we delineate the mechanisms underlying functional interplay between the E2/ERα and Rln/RXFP1 signaling pathways at the molecular and physiological levels in myometrial tissue and cells during quiescence and contractility.

2024-05-10 | GSE244842 | GEO

Relaxin Modulates the Genomic Actions and Biological Effects of Estrogen in the Myometrium [hTERT RNA-seq]

Project description:Estradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some actions of Rln, which are mediated by its membrane receptor RXFP1, require or are augmented by E2 signaling through its cognate nuclear steroid receptor, estrogen receptor alpha (ER⍺). In contrast, other actions of Rln act in opposition to the effects of E2. Here we explore the molecular and genomic mechanisms that underlie the functional interplay between E2 and Rln in the myometrium. We used both ovariectomized female mice and immortalized human myometrial cells expressing wild type or mutant ER⍺ (hTERT-HM-ER⍺ cells). Our results indicate that Rln attenuates the genomic actions and biological effects of estrogen in the myometrium and myometrial cells by reducing phosphorylation ER⍺ on serine 118 (S118). Interestingly, we observed a potent inhibitory effect of Rln on the E2-dependent binding of ER⍺ across the genome. The reduction in ER⍺ binding was associated with changes in the hormone-regulated transcriptome, including a decrease in the E2-dependent expression of neighboring genes. The inhibitory effects of Rln cotreatment on the E2-dependent phosphorylation of ER⍺ required the nuclear dual-specificity phosphatases DUSP1 and DUSP5. Moreover, the inhibitory effects of Rln were reflected in a concomitant inhibition of the E2-dependent contraction of myometrial cells. Collectively, our results identify a pathway that integrates Rln/RXFP1 and E2/ER⍺ signaling, resulting in a convergence of membrane and nuclear signaling pathways to control genomic and biological outcomes.

2024-08-31 | GSE275894 | GEO

Relaxin Attenuates the Genomic Actions and Biological Effects of Estrogens in the Myometrium by Reducing Estrogen Receptor Alpha Phosphorylation

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-05-10 | GSE244843 | GEO

Relaxin Attenuates the Genomic Actions and Biological Effects of Estrogens in the Myometrium by Reducing Estrogen Receptor Alpha Phosphorylation

Project description:Relaxin Attenuates the Genomic Actions and Biological Effects of Estrogens in the Myometrium by Reducing Estrogen Receptor Alpha Phosphorylation

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Transcription profiling of rat uterine myometrium -effect of estrogen

Project description:Uterine tissue is highly responsive to estrogen, which plays a mayor role in sympathetic innervation remodeling in myometrium; Microarrays were used to investigate which estrogen resposive myometrial proteins can be involved in innervation modulation Experiment Overall Design: Mature female rats were ovariectomized, than treated with estradiol benzoate or vechicle, myometrial samples were analyzed 6 or 24 h after treatment

2008-06-17 | E-GEOD-9117 | biostudies-arrayexpress

Expression data from rat uterine myometrium -effect of estrogen

Project description:Uterine tissue is highly responsive to estrogen, which plays a mayor role in sympathetic innervation remodeling in myometrium Microarrays were used to investigate which estrogen resposive myometrial proteins can be involved in innervation modulation Keywords: control vs. treatment, timepoints

2007-09-21 | GSE9117 | GEO

Relaxin Attenuates the Genomic Actions and Biological Effects of Estrogens in the Myometrium by Reducing Estrogen Receptor Alpha Phosphorylation [ChIP-seq]

Project description:Relaxin Attenuates the Genomic Actions and Biological Effects of Estrogens in the Myometrium by Reducing Estrogen Receptor Alpha Phosphorylation [ChIP-seq]

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Relaxin Attenuates the Genomic Actions and Biological Effects of Estrogens in the Myometrium by Reducing Estrogen Receptor Alpha Phosphorylation [RNA-seq]

Project description:Relaxin Attenuates the Genomic Actions and Biological Effects of Estrogens in the Myometrium by Reducing Estrogen Receptor Alpha Phosphorylation [RNA-seq]

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Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-diseased Myometrium

Project description:Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and from matched myometrial (MF) and fibroid (F) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1,169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFβ signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs M were not found in the F vs MF, which are likely understudied in the pathogenesis of uterine fibroids. These results suggest that the transcriptome of MF tissues are different from non-diseased myometrial tissues. Many dysregulated genes were not included in the F vs MF DEGs and may contain key genes for future investigations suggesting that fibroid studies should consider using not only matched myometrium but also non-diseased myometrium as the control.

2021-03-21 | GSE169255 | GEO

In Vivo Genome-wide PGR Binding in Pregnant Human Myometrium Identifies Potential Regulators of Labor [RNA-seq]

Project description:The alterations in myometrial biology during labor are not well understood. The myometrium is the contractile portion of the uterus and contributes to labor, a process that may be regulated by the steroid hormone progesterone. Thus, human myometrial tissues from term pregnant in-active-labor (TIL) and term pregnant not-in-labor (TNIL) subjects were used for genome-wide analyses to elucidate potential future preventive or therapeutic targets involved in the regulation of labor. Using myometrial tissues directly subjected to RNA sequencing (RNA-seq), progesterone receptor (PGR) chromatin immunoprecipitation sequencing (ChIP-seq), and histone modification ChIP-seq, we profiled genome-wide changes associated with gene expression in myometrial smooth muscle tissue in vivo. In TIL myometrium, PGR occupied predominatly promoter regions including the classical progesterone response element, whereas it bound predominantly to intergenic regions in TNIL myometrial tissue. Differential binding analysis uncovered over 1700 differential PGR-bound sites between TIL and TNIL with 1361 sites gained and 428 lost in labor. Functional analysis identified multiple pathways involved in cAMP-mediated signaling enriched in labor. A three-way integration of the data for ChIP-seq, RNA-seq and active histone marks uncovered the following genes associated with PGR binding, transcriptional activation and altered mRNA levels: ATP11A, CBX7, and TNS1. In vitro studies showed that ATP11A, CBX7, and TNS1 are progesterone responsive. We speculate that these genes may contribute to the contractile phenotype of the myometrium during various stages of labor. In conclusion, we provide novel labor associated genome-wide events and PGR-target genes that can serve as targets for future mechanistic studies.

2022-05-05 | GSE202028 | GEO

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