A Role for Orphan Nuclear Receptor Liver Receptor Homolog-1 (LRH-1, NR5A2) in Primordial Follicle Activation
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ABSTRACT:
PROVIDER: PRJNA893399 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22017992_1.fastq.gz | Fastqsanger.gz | |||
| SRR22017992_2.fastq.gz | Fastqsanger.gz | |||
| SRR22017993_1.fastq.gz | Fastqsanger.gz | |||
| SRR22017993_2.fastq.gz | Fastqsanger.gz | |||
| SRR22017994_1.fastq.gz | Fastqsanger.gz |
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Project description:The ovarian reserve of follicles comprises all oocytes for lifetime fertility and is depleted by progressive activation. The orphan nuclear receptor liver receptor homolog 1 (LRH-1; Nr5a2) is essential for ovulation, but its role in the early stages of follicular development is not known. We therefore developed a model of conditional depletion of LRH-1 from early postnatal ovaries (postnatal day 4) and performed RNAsequencing to identify LRH-1 regulated genes during the earliest stages of follicular activation.
2022-10-24 | GSE216392 | GEO
Project description:Nr5a2 (also known as liver receptor homolog-1, Lrh-1) has been shown to bind both the proximal enhancer and proximal promoter regions of Pou5f1 and regulate Pou5f1 in the epiblast stage of mouse embryonic development (Gu et al., 2005). Nr5a2-null embryos display a loss of Oct4 expression in the epiblasts (Gu et al., 2005) and die between E6.5 and E7.5 (Gu et al., 2005; Pare et al., 2004). To identify the targets of Nr5a2, we generated a stable ES cell-line that expresses HA-tagged Nr5a2. Anti-HA antibody was used to immunoprecipitate HA-Nr5a2 for ChIP-seq analysis. Keywords: Transcription factor binding sites To identify the binding sites of Nr5a2, we generated a stable ES cell-line that expresses HA-tagged Nr5a2. Anti-HA antibody was used to immunoprecipitate HA-Nr5a2.
2010-01-22 | E-GEOD-19019 | biostudies-arrayexpress
Project description:Nr5a2 (also known as liver receptor homolog-1, Lrh-1) has been shown to bind both the proximal enhancer and proximal promoter regions of Pou5f1 and regulate Pou5f1 in the epiblast stage of mouse embryonic development (Gu et al., 2005). Nr5a2-null embryos display a loss of Oct4 expression in the epiblasts (Gu et al., 2005) and die between E6.5 and E7.5 (Gu et al., 2005; Pare et al., 2004). To identify the targets of Nr5a2, we generated a stable ES cell-line that expresses HA-tagged Nr5a2. Anti-HA antibody was used to immunoprecipitate HA-Nr5a2 for ChIP-seq analysis. Keywords: Transcription factor binding sites
2010-01-22 | GSE19019 | GEO
Project description:Tumor characteristics are decisive in the determination of treatment strategy for breast cancer patients. Patients with estrogen receptor a(ERa)-positive breast cancer can benefit from long-term hormonal treatment. Nonetheless, the majority of patients will develop resistance to these therapies. Here, we investigated the role of the nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) in anti-estrogen (AE) sensitive and resistant breast cancer cells. We identified genome-wide LRH-1 binding sites using ChIP-seq, uncovering preferential binding to regions distal to transcriptional start sites (TSS). We further characterized these LRH-1 binding sites by integrating overlapping layers of specific chromatin marks, revealing that many LRH-1 binding sites are active and could be involved in long-range enhancer-promoter looping. Combined with transcriptome analysis of LRH-1 depleted cells, these results show that LRH-1 regulates specific subsets of genes involved in cell proliferation in AE-sensitive and AE-resistant breast cancer cells. Furthermore, the LRH-1 transcriptional program is highly associated with a signature of poor outcome and high-grade breast cancer tumors in vivo. Herein we report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies. ChIP-seq examination of LRH-1 binding sites with specific chromatin marks in MCF7 breast cancer cells.
2014-02-27 | E-GEOD-47027 | biostudies-arrayexpress
Project description:Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor which has been implicated in the growth and development of breast, pancreatic and colorectal cancers (CRC). In order to identify novel LRH-1-regulated genes in CRC cells, we performed gene expression profiling following siRNA-mediated LRH-1 silencing in the CRC cell line HT29.
2015-10-01 | GSE65814 | GEO
Project description:Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor which has been implicated in the growth and development of breast, pancreatic and colorectal cancers (CRC). In order to identify novel LRH-1-regulated genes in CRC cells, we performed gene expression profiling following siRNA-mediated LRH-1 silencing in the CRC cell line HCT116.
2015-10-01 | GSE65813 | GEO
Project description:Liver receptor homolog-1 (NR5A2) is expressed specifically in granulosa cells of developing ovarian follicles where it regulates the late stages of follicle development and ovulation. To establish its effects earlier in the trajectory of follicular development, NR5A2 was depleted from granulosa cells of murine primordial and primary follicles. Follicle populations were enumerated in neonates at postnatal day 4 (PND4) coinciding with the end of the formation of the primordial follicle pool. The frequency of primordial follicles in PND4 conditional knockout (cKO) ovaries was greater and primary follicles were substantially fewer relative to control (CON) counterparts. Ten-day in vitro culture of PND4 ovaries recapitulated in vivo findings and indicated that CON mice developed primary follicles in the ovarian medulla to a greater extent than did cKO animals. Two subsets of primordial follicles were observed in wildtype ovaries: one that expressed NR5A2 and the second in which the transcript was absent. Neither expressed the mitotic marker. KI-67, indicating their developmental quiescence. RNA sequencing on PND4 demonstrated that loss of NR5A2 induced changes in 432 transcripts, including quiescence markers, inhibitors of follicle activation, and regulators of cellular migration and epithelial-to-mesenchymal transition. These experiments suggest that NR5A2 expression poises primordial follicles for entry into the developing pool.
| S-EPMC7807074 | biostudies-literature
Project description:Tumor characteristics are decisive in the determination of treatment strategy for breast cancer patients. Patients with estrogen receptor a(ERa)-positive breast cancer can benefit from long-term hormonal treatment. Nonetheless, the majority of patients will develop resistance to these therapies. Here, we investigated the role of the nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) in anti-estrogen (AE) sensitive and resistant breast cancer cells. We identified genome-wide LRH-1 binding sites using ChIP-seq, uncovering preferential binding to regions distal to transcriptional start sites (TSS). We further characterized these LRH-1 binding sites by integrating overlapping layers of specific chromatin marks, revealing that many LRH-1 binding sites are active and could be involved in long-range enhancer-promoter looping. Combined with transcriptome analysis of LRH-1 depleted cells, these results show that LRH-1 regulates specific subsets of genes involved in cell proliferation in AE-sensitive and AE-resistant breast cancer cells. Furthermore, the LRH-1 transcriptional program is highly associated with a signature of poor outcome and high-grade breast cancer tumors in vivo. Herein we report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies.
2014-02-27 | GSE47027 | GEO
Project description:Chronic endoplasmic reticulum (ER) stress results in toxicity that contributes to multiple human disorders. We report a stress resolution pathway initiated by the nuclear receptor LRH-1 that is independent of known unfolded protein response (UPR) pathways. Like mice lacking primary UPR components, hepatic Lrh-1-null mice cannot resolve ER stress, despite a functional UPR. In response to ER stress, LRH-1 induces expression of the kinase Plk3, which phosphorylates and activates the transcription factor ATF2. Plk3-null mice also cannot resolve ER stress, and restoring Plk3 expression in Lrh-1-null cells rescues ER stress resolution. Reduced or heightened ATF2 activity also sensitizes or desensitizes cells to ER stress, respectively. LRH-1 agonist treatment increases ER stress resistance and decreases cell death. We conclude that LRH-1 initiates a novel pathway of ER stress resolution that is independent of the UPR, yet equivalently required. Targeting LRH-1 may be beneficial in human disorders associated with chronic ER stress. 24 total samples. One sample represents one mouse. Three samples were analyzed from the following groups: Lrh-1 f/f (control littermates) treated with vehicle, Lrh-1 f/f treated with tunicamycin (TM; 1mg/kg BW for 24h), Lrh-1 f/f treated with tunicamycin and DLPC (100mg/kg BW 4x), Lrh-1 f/f treated with tunicamycin and vehicle for DLPC, Lrh-1 liver-specific KO mice (LKO) treated with vehicle, Lrh-1 LKO treated with tunicamycin, and Lrh-1 LKO treated with tunicamycin and DLPC, Lrh-1 LKO treated with tunicamycin and vehicle for DLPC
2015-05-12 | E-GEOD-68718 | biostudies-arrayexpress
Project description:Chronic endoplasmic reticulum (ER) stress results in toxicity that contributes to multiple human disorders. We report a stress resolution pathway initiated by the nuclear receptor LRH-1 that is independent of known unfolded protein response (UPR) pathways. Like mice lacking primary UPR components, hepatic Lrh-1-null mice cannot resolve ER stress, despite a functional UPR. In response to ER stress, LRH-1 induces expression of the kinase Plk3, which phosphorylates and activates the transcription factor ATF2. Plk3-null mice also cannot resolve ER stress, and restoring Plk3 expression in Lrh-1-null cells rescues ER stress resolution. Reduced or heightened ATF2 activity also sensitizes or desensitizes cells to ER stress, respectively. LRH-1 agonist treatment increases ER stress resistance and decreases cell death. We conclude that LRH-1 initiates a novel pathway of ER stress resolution that is independent of the UPR, yet equivalently required. Targeting LRH-1 may be beneficial in human disorders associated with chronic ER stress.
2015-05-12 | GSE68718 | GEO