H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition [ChIP-seq]
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ABSTRACT:
PROVIDER: PRJNA415198 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition
| PRJNA415202 | ENA
Project description:Uncovering the causes of pregnancy complications such as preterm labor requires greater insight into how the uterus remains in a non-contractile state until term and then surmounts this state to enter labor. Here, we show in mice that dynamic deposition and removal of repressive H3K27me3 chromatin marks in decidual stromal cells dictate both elements of pregnancy success. In early gestation, H3K27me3-induced transcriptional silencing of select gene targets insures uterine quiescence by preventing the decidua from expressing parturition-inducing hormone receptors, manifesting type 1 immunity, and, most unexpectedly, generating myofibroblasts and associated wound healing responses. In late gestation, genome-wide H3K27 demethylation allows for target gene upregulation, decidual activation, and labor entry. Strikingly, pharmacological inhibition of this latter process not only prevented term parturition, but also inhibited delivery while maintaining pup viability in a non-inflammatory model of preterm parturition. Immunofluorescence analysis of human specimens suggested that similar regulatory events might occur in the human decidua. Together, these results reveal the centrality of regulated gene silencing in the uterine adaptation to pregnancy and suggest new areas in the study and treatment of pregnancy disorders.
2017-10-23 | GSE105455 | GEO
Project description:Uncovering the causes of pregnancy complications such as preterm labor requires greater insight into how the uterus remains in a non-contractile state until term and then surmounts this state to enter labor. Here, we show in mice that dynamic deposition and removal of repressive H3K27me3 chromatin marks in decidual stromal cells dictate both elements of pregnancy success. In early gestation, H3K27me3-induced transcriptional silencing of select gene targets insures uterine quiescence by preventing the decidua from expressing parturition-inducing hormone receptors, manifesting type 1 immunity, and, most unexpectedly, generating myofibroblasts and associated wound healing responses. In late gestation, genome-wide H3K27 demethylation allows for target gene upregulation, decidual activation, and labor entry. Strikingly, pharmacological inhibition of this latter process not only prevented term parturition, but also inhibited delivery while maintaining pup viability in a non-inflammatory model of preterm parturition. Immunofluorescence analysis of human specimens suggested that similar regulatory events might occur in the human decidua. Together, these results reveal the centrality of regulated gene silencing in the uterine adaptation to pregnancy and suggest new areas in the study and treatment of pregnancy disorders.
2017-10-23 | GSE105444 | GEO
Project description:H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition [RNA-seq]
| PRJNA415206 | ENA
Project description: Not available
| S-EPMC5749543 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-10-23 | GSE105456 | GEO
Project description:To define the vast landscape of mice pregnancy and labor/parturition associated gene expression transitions, wild type FVB mice uterine tissues from the non-pregnant state (NP) and at E6.5, E8.5, E10.5, E15.5 and E17.5 were analysed using gene expression microarray
2018-11-07 | GSE85934 | GEO
Project description:The process of parturition involves the complex interplay of factors that changes the excitability and contractile activity of the uterus. We have compared the relative gene expression profile of myometrium from rats before parturition (21 days pregnant) and during delivery using high-density DNA microarray. Of 8740 sequences available in the array a total of 3782 were detected as present. From the sequences that were significantly altered, 59 genes were upregulated and 82 genes were downregulated. We were able to detect changes in genes described to have altered expression level at term including connexin 43 and 26, cyclo-oxygenase 2 and oxytocin receptor as well as novel genes that have been not previously associated with parturition. Quantitative real time PCR on selected genes further confirmed the microarray data. Here we report for the first time that aquaporin5 (AQP5), a member of aquaporin (AQP) water channel family, was dramatically downregulated during parturition (~100 fold by microarray and ~50 fold by Real Time PCR). The emerging profile highlights biochemical cascades occurring in a period of about 36 hours that triggers parturition and the initiation of myometrium reverse remodeling after partum. The microarray analysis uncovered genes that were previously suspected to play a role in parturition. This regulation involves genes from immune/inflammatory response, steroid/lipids metabolism, calcium homeostasis, cell volume regulation, cell signaling, cell division, and tissue remodeling, suggesting the presence of multiple and redundant mechanisms altered in the process of birth. Experiment Overall Design: Uteri were dissected from late pregnant rats (21 days, LP) (three individuals, two replicates of sample 1) and rats during labor (DL) after the expulsion of the second pup (three individuals, two replicates of sample 1). After dissection, uteri were placed immediately in cold Ca2+-free PBS buffer and peripheral large blood vessels, external surrounding connective tissue and placenta were removed. The endometrium superficial layer was separated by gentle scraping. The myometrium was weighted, finely minced and homogenized with a polytron (Polytron PT3000, Brinkmann, Switzerland).
2008-10-25 | E-GEOD-12799 | biostudies-arrayexpress
Project description:The process of parturition involves the complex interplay of factors that changes the excitability and contractile activity of the uterus. We have compared the relative gene expression profile of myometrium from rats before parturition (21 days pregnant) and during delivery using high-density DNA microarray. Of 8740 sequences available in the array a total of 3782 were detected as present. From the sequences that were significantly altered, 59 genes were upregulated and 82 genes were downregulated. We were able to detect changes in genes described to have altered expression level at term including connexin 43 and 26, cyclo-oxygenase 2 and oxytocin receptor as well as novel genes that have been not previously associated with parturition. Quantitative real time PCR on selected genes further confirmed the microarray data. Here we report for the first time that aquaporin5 (AQP5), a member of aquaporin (AQP) water channel family, was dramatically downregulated during parturition (~100 fold by microarray and ~50 fold by Real Time PCR). The emerging profile highlights biochemical cascades occurring in a period of about 36 hours that triggers parturition and the initiation of myometrium reverse remodeling after partum. The microarray analysis uncovered genes that were previously suspected to play a role in parturition. This regulation involves genes from immune/inflammatory response, steroid/lipids metabolism, calcium homeostasis, cell volume regulation, cell signaling, cell division, and tissue remodeling, suggesting the presence of multiple and redundant mechanisms altered in the process of birth.
2008-09-23 | GSE12799 | GEO
Project description:Uterine contractile dysfunction leads to pregnancy complications such as preterm birth and labor dystocia. Progesterone is necessary to suppress uterine contractions to prevent premature labor. As humans maintain high levels of progesterone throughout parturition, a functional progesterone withdrawal hypothesis suggests that relative levels of myometrial progesterone receptor isoforms PGR-A and PGR-B switch at parturition, where PGR-B promotes a relaxed state and PGR-A result in increased uterine contractility. Our objective is to determine the effects of altered levels of PGR-B and PGR-A in the mouse myometrium on pregnancy and parturition using transgenic mouse models in which the relative levels of these isoforms are altered specifically in the myometrium. Overexpression of PGR-B is associated with a markedly increased gestational length compared to control mice. In both ex vivo and in vivo experiments, myometrium of PGR-B overexpressing mice have prolonged labor, a significant decrease in uterine contractility, and a high incidence of labor dystocia. Conversely, overexpression of PGR-A is associated with an increase in uterine contractility without a change in gestational length. Uterine RNAseq at mid-pregnancy identified isoform-specific downstream targets and genes that were commonly regulated by both PGR isoforms. Gene signature analyses further revealed that PGR-B promotes muscle relaxation and that PGR-A is pro-inflammation. High levels of PGR-B manifest a genetic profile of a blunted phospholipase C pathway that mediates oxytocin and angiotensin II induced muscle contraction. These findings provided in vivo support that PGR isoform levels determine distinct transcriptomic landscapes and pathways in myometrial function and labor.
2021-02-24 | GSE146634 | GEO