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Genome-wide Profiling of FOXA2 and POL2 binding in the mouse uterus [ChIP-Seq]

ABSTRACT: Forkhead box A2 (FOXA2) is a critical regulator of endometrial gland development in mice. In the adult mouse uterus, FOXA2 is expressed solely in the GE cells of the endometrium. Conditional deletion of Foxa2 after birth in the uterus, using the progesterone receptor Cre mouse (PgrCre), impeded gland development, thereby rendering the adult mouse infertile due to defects in blastocyst implantation stemming from a lack of endometrial glands and their secretions. As a first step to begin understanding the FOXA2 function in the endometrial glands of the uterus, genome-wide investigation of in vivo FOXA2 and RNA polymerase II (POL2) binding target regions in the neonatal and adult uterus was determined by chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq).

ORGANISM(S): Mus musculus

PROVIDER: GSE48238 | GEO | 2013/12/01

SECONDARY ACCESSION(S): PRJNA209329

REPOSITORIES: GEO

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Genome-wide Profiling of FOXA2 and POL2 binding in the mouse uterus [ChIP-Seq]

Project description:Forkhead box A2 (FOXA2) is a critical regulator of endometrial gland development in mice. In the adult mouse uterus, FOXA2 is expressed solely in the GE cells of the endometrium. Conditional deletion of Foxa2 after birth in the uterus, using the progesterone receptor Cre mouse (PgrCre), impeded gland development, thereby rendering the adult mouse infertile due to defects in blastocyst implantation stemming from a lack of endometrial glands and their secretions. As a first step to begin understanding the FOXA2 function in the endometrial glands of the uterus, genome-wide investigation of in vivo FOXA2 and RNA polymerase II (POL2) binding target regions in the neonatal and adult uterus was determined by chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq). In order to determine the transcriptional regulatory networks mediating FOXA2 regulation of endometrial gland development and function, chromatin immunoprecipitation and massively parallel sequencing (ChIP-Seq) was used to create a genome-wide profile of in vivo FOXA2-binding sites in the developing (PD 12) and adult (DOPP 2.5 and 3.5) mouse uterus.

2013-12-01 | E-GEOD-48238 | biostudies-arrayexpress

Determination of the Forkhead box A2 (FOXA2) Cistrome in the Human Endometrium

Project description:Uterine glands are central to endometrial function and fertility, however the mechanisms regulating their development and function are not well understood. The pioneer forkhead box A2 (FOXA2) transcription factor is distinctively expressed in the glands of the endometrium in both the human and mouse uterus. Studies in mice established that FOXA2 is a critical regulator of gland development in the neonatal uterus as well as differentiated gland function in the adult uterus. An integrative approach was used here to define the FOXA2 cistrome in the human endometrium. Genome-wide mapping of FOXA2 binding sites by chromatin immunoprecipitation sequencing (ChIP-Seq) was performed on proliferative (P) and mid-secretory (MS) phase endometrium and combined with the transcriptome determined by RNA sequencing (RNA-Seq). Distinctive binding of FOXA2 was observed between the P and MS endometrium, and FOXA2 binding intervals were enriched for different transcription factor binding motifs between the phases of endometrium. Pathway analysis revealed different biological processes regulated by FOXA2 bound genes in the P and MS endometrium. Thus, FOXA2 is proposed to regulate gene expression in concert with other transcription factors to influence gland function in a cycle phase-dependent manner. Further analysis identified potential FOXA2 regulated genes that influence endometrial growth, uterine receptivity, and stromal cell decidualization. This analysis of the FOXA2 cistrome provides a foundation essential to understanding fundamental aspects of uterine gland development, differentiation, function, and disease.

2018-08-30 | GSE119209 | GEO

Sexually dimorphic effects of forkhead box a2 (FOXA2) and uterine glands on decidualization and fetoplacental development

Project description:Glands of the uterus are essential for the establishment of pregnancy in mice, sheep and likely humans. Forkhead box a2 (FOXA2) is expressed specifically in the glands of the uterus and a critical regulator of glandular epithelium (GE) differentiation, development and function. Mice with a conditional deletion of FOXA2 in the adult uterus, created using the lactotransferrin iCre (Ltf-iCre) model, have a morphologically normal uterus with glands, but lack a considerable number of FOXA2-dependent GE-expressed genes. Adult FOXA2 conditional knockout (cKO; Ltf-iCre:Foxa2 flox) mice are infertile due to defective embryo implantation arising from a lack of leukemia inhibitory factor (LIF), a critical implantation factor of uterine gland origin. Intraperitoneal injections of LIF can initiate embryo implantation in the uterus of adult FOXA2 cKO mice with pregnancies maintained to term. Here, we tested the hypothesis that FOXA2-regulated genes in the uterine glands impact development of the decidua, placenta and fetus. On gestational day (GD) 8.5, the anti-mesometrial and mesometrial decidua transcriptome was noticeably altered in FOXA2 cKO mice. Viable fetuses were reduced in FOXA2 cKO mice on GDs 12.5 and 17.5. Sex-dependent differences in fetal weight, placenta histoarchitecture, and the placenta and metrial gland transcriptome were observed between control and FOXA2 cKO mice. The transcriptome of the placenta with a female fetus was considerably more altered than the placenta with a male fetus in FOXA2 cKO dams. These studies reveal previously unrecognized sexually dimorphic effects of FOXA2 and uterine glands on fetoplacental development with potential impacts on offspring health into adulthood.

2020-07-09 | GSE154026 | GEO

Project description:FOXA2-regulated genes in the adult mouse uterus

| PRJNA209720 | ENA

Uterine glands synchronize embryo-endometrial interactions and coordinate on-time embryo implantation and stromal cell decidualization for pregnancy success

Project description:By employing FOXA2-deficient mouse models coupled with LIF repletion, we reveal definitive roles of uterine glands in pregnancy establishment.These studies provide original evidence that uterine glands synchronize embryo-endometrial interactions, coordinate on-time embryo implantation, and impact stromal cell decidualization, thereby ensuring embryo viability, placental growth, and pregnancy success.

2018-04-13 | GSE113065 | GEO

Identification of candidate FOXA2-regulated genes in the adult mouse uterus

Project description:To identify candidate genes regulated by forkhead transcription factor box A2 (FOXA2) in the uterus, control and Foxa2-deleted uteri were collected at day of pseudopregnancy (DOPP) 3.5 (DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the Foxa2-deleted as compared to control uteri that are candidiate FOXA2-regulated genes in the uterus. Whole uteri (control wild type n=4; Foxa2-deleted n=4) were analyzed for differences in their transcriptome using a mouse microarray.

2013-12-01 | E-GEOD-48339 | biostudies-arrayexpress

Overexpression of FOXL2 altered uterine structures and functions

Project description:Pgrcre/+Foxl2LsL/+ mice showed absence of corpus luteum in the ovary, thus the mice were infertile and continuously at diestrus stage with very thin uterus. Multiple uterine defects were observed. The gland number and penetratioin to the stroma were decreased, and the epithelial stratification and the collagen deposition in the stroma were increased. The whole uterus were collected from 12 weeks old control and mutant mice at diestrus stage for RNA-sequencing. In total, 3515 genes were differentially expressed, with 1746 upregulated and 1769 genes downregulated in the mutant mice. Pathways related to extracellular matrix, gland formation, cell proliferation were altered. The muntant mice transcriptomic changes was significantly postively correlated with the human endometriosis transcrptomic changes.

2020-11-06 | GSE140047 | GEO

Mus musculus

Project description:Identification of candidate FOXA2-regulated genes in the adult mouse uterus

| PRJNA209723 | ENA

Analysis of Porcupine ablation within the uterine epithelium on gene expression within the uterus

Project description:The secretion of mammalian Wnt Ligands within the cell is dependent on the activity of Porcupine, a gene located on the X chromosome that encodes for a membrane bound o-acyl transferase. Porcupine-dependent Wnt signalling was previously shown to be essential for the post-natal maintenance of endometrial glands, structures that are essential for implantation and fertility. Previous data has implicated the multiple members of the Wnt family expressed in the female uterus to be involved in a coordinated crosstalk between the luminal and stromal compartments of the uterus, ensuring the proper development of the uterus and successful fertility. We have generated a conditional mutant of Porcupine in the luminal epithelium (cKOepi) of the uterus, thus eliminating Wnt7a/b and Wnt11, to address the nature of this crosstalk. Unlike global luminal-stromal mutants, post-natal ablation of Porcupine in the luminal epithelium alone does not affect the maintenance of the endometrial glands in adults. Uterine glands are still visible in the adult cKOepi, albeit in a smaller number than that of control uteri. Despite having uterine glands, cKOepi females remain completely infertile. We have attributed the sterility of these females to be in part due to defects in implantation and decidualization; cKOepi fail to respond to decidual induction by artificial means. Interestingly, progesterone supplementation rescues the observed implantation defects, although observed decidual soon seem to become resorptive. Microarray analysis of cKOepi during implantation has reveals several potential targets for luminal WNT that may be responsible for the observed phenotype including: Lef1, Hoxa10, Wnt4, Wnt16 Notch1, Notch4 and Dll4 .

2017-03-21 | GSE96801 | GEO

Expression data from P14 Lgr5-2A-EGFP mouse uterus

Project description:Epithelial gland development within the uterine lining during prepubertal period is important to ensure successful gestation in adults. Lgr5 expression in uterus becomes largely restricted to the tips of developing glands after birth. These Lgr5 highly expressing cells function as stem cells during gland development. We used microarrays to detail the gene expression profilings and compare between Lgr5 highly and negatively expressing cells in developing uterus.

2019-09-26 | GSE137974 | GEO

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