Tissue-specific progesterone receptor-chromatin binding and the regulation of progesterone-dependent gene expression
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE115820 | GEO | 2018/12/01
REPOSITORIES: GEO
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Project description:RUNX1 is induced by the LH surge in the ovary and plays an important role in granulosa cells in the peri-ovulatory window through the induction of key gene expression. The ablation of the canonical heterodimer partner of RUNX1 (CBFβ) leads to ovulatory failure and subfertility in female mice. A possible interaction between RUNX1 and PGR on the chromatin level has also been indicated. However, the properties of RUNX1 chromatin binding in granulosa cells in response to the LH surge remains unknown. This study aims to characterise the RUNX1 cistrome in pre- and peri-ovulatory granulosa cells and explore the potential interaction between RUNX1 and the key ovulatory factor PGR.
2021-06-22 | GSE152941 | GEO
Project description:Ovulation is triggered by the gonadotropin surge that induces the expression of two key genes, progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2) in the granulosa cells of preovulatory follicles. Their gene products PGR and PTGS2 activate two separate pathways that are both essential for successful ovulation. Here we show that the PGR plays an additional essential role; attenuate ovulatory inflammation by diminishing the gonadotropin surge-induced Ptgs2 expression. PGR indirectly terminates Ptgs2 expression and PGE2 synthesis in granulosa cells by inhibiting the NF-κB, a transcription factor required for Ptgs2 expression. When the expression of PGR was ablated in the granulosa cells, the ovary undergoes hyperinflammatory condition manifested by excessive PGE2 synthesis, immune cell infiltration, oxidative damage, and neoplastic transformation of ovarian cells. Despite the ovary undergoes ovulations dozens or hundreds of times in one’s lifetime, the repetitive ovulatory inflammations do not leave significant tissue damage in the ovary. The PGR-driven termination of PTGS2 expression may protect ovary from the ovulatory inflammation.
2020-03-07 | GSE145107 | GEO
Project description:Progesterone receptor (PGR) is essential for various functions in the female reproductive tract, especially ovulation in the ovary. PGR consists of two main isoforms, PGR-A and PGR-B, that possess different expression patterns and are responsible for various unique roles in different tissue contexts. While both are present in the reproductive tract, PGR-A is the only one known to be essential for ovulation while PGR-B plays a lesser role in the reproductive tract. However, the specific roles of PGR isoforms on gene expression in peri-ovulatory granulosa cells have not been previously investigated in detail. In this study, we identified the unique role of PGR-A and PGR-B in peri-ovulatory granulosa cells through RNA-seq of knockout mouse models for total PGR (PGR KO) or specific isoforms (PGR-A KO and PGR-B KO)
2022-05-18 | GSE168213 | GEO
Project description:Ovulation requires sequential molecular events and structural remodeling in the ovarian follicle for the successful release of a mature oocyte capable of being fertilised. Critical to this process is progesterone receptor (PGR), a transcription factor highly yet transiently expressed in granulosa cells of preovulatory follicles. Progesterone receptor knockout (PRKO) mice are anovulatory, with a specific and complete defect in follicle rupture. Therefore, this model was used to examine the critical molecular and biochemical mechanisms necessary for successful ovulation. We used microarrays to identify putative PGR-regulated genes in granulosa cells at a time when PGR expression is maximal (eCG + 8h hCG) and the preovulatory follicle is undergoing the final changes necessary for successful ovulation.
2018-04-20 | GSE92437 | GEO
Project description:Ovulation requires sequential molecular events and structural remodeling in the ovarian follicle for the successful release of a mature oocyte capable of being fertilised. Critical to this process is progesterone receptor (PGR), a transcription factor highly yet transiently expressed in granulosa cells of preovulatory follicles. Progesterone receptor knockout (PRKO) mice are anovulatory, with a specific and complete defect in follicle rupture. Therefore, this model was used to examine the critical molecular and biochemical mechanisms necessary for successful ovulation. Although PGR is not expressed in the cumulus cells or oocyte of the preovulatory cumulus oocyte complex (COC), it is well known that the COC responds to the cascade of gene expression changes that occurs in preovulatory granulosa cells. We used microarrays to identify putative ‘ovulation’ genes in preovulatory COCs at a time when PGR expression is maximal in granulosa cells (eCG + 8h hCG) and the preovulatory COC and follicle are undergoing the final changes necessary for successful ovulation.
2018-04-20 | GSE92436 | GEO
Project description:The oviducts play a critical role in gamete and embryo transport, as well as supporting fertilization and early embryo development. Progesterone receptor (PGR) is a transcription factor highly expressed in oviductal cells, while it’s activating ligand, progesterone (P4), surges to peak levels as ovulation approaches. P4 is known to regulate oviduct cilia beating and muscular contractions in vitro, but how PGR may mediate this in vivo is poorly understood. We used PGR-knockout (PRKO) mice to determine how PGR regulates oviductal function during the periovulatory period, in particular oviductal transport and embryo support. We used microarrays to identify putative PGR-regulated genes in the oviduct during the periovulatory period, a time when the oviduct is preparing to receive the newly-ovulated COC. The mutant strain used in this experiment were PRlacZ knock-in mice which originated from Assoc Prof John Lydon, Baylor College of Medicine, Houston TX, USA. The lacZ insertion results in disruption of transcription of both isoforms of PGR (Ismail et al, 2002, Mol Endocrinol 16:2475-2489), and therefore mice homozygous for the lacZ insertion are a phenocopy of the knockout strain described by Lydon et al. (1995, Genes Dev. 9:2266-2278) and are hereafter referred to as PRKO. Heterozygous mice (PR+/-) are a phenocopy of WT and have normal fertility (Ismail et al, 2002) and are therefore appropriate controls. Whole oviducts were collected from pre-pubertal PRKO and PR+/- mice 8 h after a standard protocol for hormonal induction of ovulation. Day 21-23 old mice were injected i.p. with 5IU of equine chorionic gonadotropin (eCG) to stimulate follicle growth, followed 44-47 h later by i.p. injection of 5 IU of human chorionic gonadotropin (hCG) to trigger ovulatory processes. Oviducts from 15 animals were collected per genotype, with oviducts from 3 animals pooled per sample for a total of n = 5 samples per genotype.
2014-06-16 | E-GEOD-51499 | biostudies-arrayexpress
Project description:During ovulation, the LH surge leads to the activation of various signalling cascades in granulosa cells, resulting in a critical shift in chromatin landscape and correspondingly the ovarian gene expression profile. Such large-scale genomic reprogramming involves a specific suite of ovulatory transcription factors. An essential factor for ovulation is the progesterone receptor (PGR). One of the ways through which PGR can mediate transcription regulation is through interaction with histone and chromatin remodellers to facilitate chromatin reprogramming and thereby enabling transcription. However, it is unknown whether this mechanism is employed by PGR in granulosa cells. This study aims to characterise global changes in the chromatin landscape that are induced by the LH surge and to determine the role of PGR in facilitating chromatin accessibility in granulosa cells during ovulation.
2022-02-15 | GSE166878 | GEO
Project description:We report the genome-wide binding sites of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells that express either PGR-A or PGR-B. Progesterone, acting through the progesterone receptors (PGRs), is one of the most critical regulators of endometrial differentiation, known as decidualization, which is a key step toward the establishment of pregnancy. Yet a long-standing unresolved issue in uterine biology is the precise roles played by the major PGR isoforms, PGR-A and PGR-B, during decidualization in the human. Our approach, expressing PGR-A and PGR-B individually after silencing endogenous PGRs in human endometrial stromal cells (HESC), enabled the analysis of the roles of these isoforms separately as well as jointly by ChIP-seq and gene-expression analysis. In order to study the cistromes of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells, we generated primary cultures of human endometrial stromal cells expressing flag tagged PGR-A and PGR-B individually after silencing endogenous PGRs. Input DNA was used as the reference sample.
2015-04-27 | E-GEOD-62475 | biostudies-arrayexpress
Project description:Chromatin immunoprecipitation-based sequencing (ChIP-seq) of H3K27Ac was performed using mouse ovarian granulosa cells before and after ovulatory signal stimulation. We found genome-wide H3K27Ac was erased rapidly at 1h after hCG treatment, and new H3K27Ac was established at 4h after hCG treatment.
2021-01-30 | GSE165809 | GEO
Project description:Chromatin immunoprecipitation for the progesterone receptor (PGR) and sequencing was performed on Pgrcre/-mPRALsL/+ mice. These mice exhibit no endogenous PGR expression, yet exhibit constitutive expression of the PGR-A isoform in PGR positive tissues due to the presence of a conditional expression allele. Mice were ovariectomized, rested for two weeks, and treated with progesterone for 1 hour before harvesting and freezing whole uterine tissue.
2019-08-29 | GSE86314 | GEO