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FOXL2 and ESR1 binding sites in primary cells from mouse ovarian follicles

ABSTRACT: It has previously been shown that FOXL2 and ESR1 cooperate to repress the testis-determining gene Sox9 in murine granulosa cells, and suggested that FOXL2/ESR1 cooperation may be central to granulosa cell differentiation (Uhlenhaut et al., 2009). However, no study has so far compared the DNA-binding of FOXL2 and ESR1 at the genomic level or analyzed the impact of FOXL2 on ESR1 binding to its regulatory elements. Here, we have analyzed and compared the genomic locations recognized by ESR1 and FOXL2 in E2-treated primary murine granulosa cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE62545 | GEO | 2015/07/01

SECONDARY ACCESSION(S): PRJNA264380

REPOSITORIES: GEO

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FOXL2 and ESR1 binding sites in primary cells from mouse ovarian follicles

Project description:It has previously been shown that FOXL2 and ESR1 cooperate to repress the testis-determining gene Sox9 in murine granulosa cells, and suggested that FOXL2/ESR1 cooperation may be central to granulosa cell differentiation (Uhlenhaut et al., 2009). However, no study has so far compared the DNA-binding of FOXL2 and ESR1 at the genomic level or analyzed the impact of FOXL2 on ESR1 binding to its regulatory elements. Here, we have analyzed and compared the genomic locations recognized by ESR1 and FOXL2 in E2-treated primary murine granulosa cells. Input DNA, FOXL2 and ESR1 ChIP

2015-07-01 | E-GEOD-62545 | biostudies-arrayexpress

FOXL2 interaction with different binding partners regulates the dynamics of granulosa cell differentiation across ovarian development

Project description:FOXL2 is a transcription factor essential for female fertility, expressed in somatic cells of the ovary, notably granulosa cells. In the mouse, Foxl2 deletion leads to partial sex reversal postnatally. However, deletion of the gene in 8-week-old females leads to granulosa to Sertoli cell transdifferentiation. We hypothesised that different outcomes of Foxl2 deletion in embryonic versus adult ovary may depend on a different role played across ovarian development. Therefore, we characterised the dynamics of gene expression and chromatin accessibility changes in purified murine granulosa cells across key developmental stages (E14.5, 1 and 8 weeks). We then performed genome-wide identification of FOXL2 target genes and on-chromatin interacting partners by ChIP-SICAP. We found that FOXL2 regulates more genes at postnatal stages, through the interaction with factors regulating primordial follicle activation (PFA), such as NR5A2, and others regulating steroidogenesis including AR and ESR2. As a proof of principle experiment, we chose one FOXL2 interactor, Ubiquitin specific protease 7 (USP7) and showed that deletion of this gene in granulosa cells leads to a blockage of PFA, impaired ovary development and sterility. Our study constitutes a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.

2024-03-25 | PXD043951 | Pride

Transcription profiling of mouse KK1 granulosa cells transfected with Foxl2-VP16 and Foxl2-MAD

Project description:The Foxl2 transcription factor is required for ovarian function during follicular development. Our approach to begin to understand Foxl2 function is through the identification of Foxl2 regulated genes in the ovary. Transiently transfected KK1 mouse granulosa cells were used to identify genes that are potentially regulated by Foxl2. KK1 cells were transfected in three groups (mock, activated, and repressed) and twenty-four hours later RNA was isolated and submitted for Affymetrix microarray analysis. Experiment Overall Design: To increase the potential of Foxl2 to alter gene expression levels of putative target genes, two fusions were constructed consisting of Foxl2 fused to the activation domain of the Herpes simplex virus VP16 transcription factor (Foxl2-VP16) and Foxl2 fused to the repression domain of the murine MAD transcription factor (Foxl2-MAD). Levels of gene expression were compared between mock transfected cells and those that were transfected with Foxl2-VP16 and Foxl2-MAD, respectively.

2009-11-15 | E-GEOD-18891 | biostudies-arrayexpress

Transcriptome Sequencing Revealed that Knockdown of FOXL2 Affects Cell Proliferation, Cycle, and DNA Replication in Chicken pre-ovulatory Follicles Cells

Project description:Forkhead box L2 (FOXL2) is a single-exon gene encoding a forkhead transcription factor, which is mainly expressed in the ovary, eyelids and pituitary gland. FOXL2 plays an essential role in ovarian development. To reveal the effects of FOXL2 on biological process and gene expression of ovarian granulosa cells (GCs), we established stable FOXL2-knockdown GCs and then analyzed using transcriptome sequencing. It is observed that knockdown the FOXL2 affects the biological processes of cell proliferation, DNA replication, apoptosis and cell cycle. In which, the FOXL2 knockdown promoted cell proliferation and DNA replication, decreased cell apoptosis, and promoted mitosis. In addition, by comparing the transcriptome by FOXL2 knockdown, we found a serious of DEGs and their related pathways. These results indicated that, through mediating these genes and pathways, the FOXL2 might induce the cell proliferation, cycle, and DNA replication, and play a key role during ovarian development and maintenance.

2020-06-20 | GSE148533 | GEO

FOXL2 binding sites in primary cells from mouse ovarian follicles

Project description:FOXL2 is a lineage determining transcription factor in the ovary, but its direct targets and modes of action are not fully characterized. Here, we explore the genomic targets of FOXL2. We found in particular that FOXL2 directly modulates Esr2 expression through a newly identified intronic element. Input DNA and FOXL2 ChIP

2014-10-29 | E-GEOD-60858 | biostudies-arrayexpress

The oncogenic FOXL2 mutation C134W is the sole driver of granulosa cell tumors in mice

Project description:We have generated a humanized Foxl2 mouse model by genome editing to evaluate in vivo the role of mutated FOXL2 in the development of murine Adult Granulosa Cell Tumors

2023-01-31 | GSE202242 | GEO

FOXL2 binding sites in primary cells from mouse ovarian follicles

2014-10-29 | GSE60858 | GEO

A genome-wide exploration of the targets of the transcription factors FOXL2 and ESR2 unveils their implication in cell migration, invasion and adhesion [RNA-Seq]

Project description:We depleted Foxl2 or Esr2 in murine primary granulosa cells and assessed the molecular consequences at the transcrit levels. We show that FOXL2 is involved in a large number of regulatory actions essential for the maintenance of cell fate of granulosa cells. We confirm that FOXL2 and ESR2 modulate, directly of through a coherent feed-forward loop, an important number of common targets.

2021-03-24 | GSE154185 | GEO

Identification of protein co-localized with Foxl2 on chromatin

Project description:Foxl2 is a forkhead transcription factor essential for proper reproductive function in females. It is expressed in the somatic cell population of the gonad (granulosa cells) which forms the follicles of the ovary, the structures responsible for embedding and nurturing the oocytes during their development. FOXL2 directly regulate the aromatase that synthesizes estrogens CYP19A1, thus promoting female differentiation, as well as acting as a repressor of the male factors SOX9 and DMRT1.Expression is also found in the eyelids, pituitary gland and uterus. In the goat, frog and many fish species FOXL2 is a sex-determining gene which, when deleted, leads to female-to-male sex reversal.

2022-07-11 | PXD024439 | Pride

Effect of depletion of FOXL2 on gene expression in KGN cells

Project description:To investigate the targets of FOXL2 in human granulosa cells, we performed Knock-Down experiment in established homozygous cell lines for FOXL2 WT (KGN).

2023-11-06 | GSE227040 | GEO

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