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Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells [RNA-Seq]

ABSTRACT: Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells [RNA-Seq]

PROVIDER: PRJNA640277 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12042900_1.fastq.gz	Fastqsanger.gz
	SRR12042900_2.fastq.gz	Fastqsanger.gz
	SRR12042901_1.fastq.gz	Fastqsanger.gz
	SRR12042901_2.fastq.gz	Fastqsanger.gz
	SRR12042902_1.fastq.gz	Fastqsanger.gz

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Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells [ChIP-seq]

Project description:This study reports androgen-induced gene expression in granulosa cells of the ovary and provides a molecular insight of how androgens regulate granulosa cell gene expression through modulating the epigenetic mark H3K27me3.

2020-06-19 | GSE152791 | GEO

Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells [RNA-Seq]

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Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells

Project description:Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells

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Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells [ChIP-seq]

Project description:Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells [ChIP-seq]

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Androgens Regulate Ovarian Gene Expression through Modulation of H3K27me3 in Granulosa Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-06-19 | GSE152792 | GEO

Androgens regulate ovarian gene expression by balancing Ezh2-Jmjd3 mediated H3K27me3 dynamics.

Project description:Conventionally viewed as male hormone, androgens play a critical role in female fertility. Although androgen receptors (AR) are transcription factors, to date very few direct transcriptional targets of ARs have been identified in the ovary. Using mouse models, this study provides three critical insights about androgen-induced gene regulation in the ovary and its impact on female fertility. First, RNA-sequencing reveals a number of genes and biological processes that were previously not known to be directly regulated by androgens in the ovary. Second, androgens can also influence gene expression by decreasing the tri-methyl mark on lysine 27 of histone3 (H3K27me3), a gene silencing epigenetic mark. ChIP-seq analyses highlight that androgen-induced modulation of H3K27me3 mark within gene bodies, promoters or distal enhancers have a much broader impact on ovarian function than the direct genomic effects of androgens. Third, androgen-induced decrease of H3K27me3 is mediated through (a) inhibiting the expression and activity of Enhancer of Zeste Homologue 2 (EZH2), a histone methyltransferase that promotes tri-methylation of K27 and (b) by inducing the expression of a histone demethylase called Jumonji domain containing protein-3 (JMJD3/KDM6B), responsible for removing the H3K27me3 mark. Androgens through the PI3K/Akt pathway, in a transcription-independent fashion, increase hypoxia-inducible factor 1 alpha (HIF1α) protein levels, which in turn induce JMJD3 expression. Furthermore, proof of concept studies involving in vivo knockdown of Ar in the ovary and ovarian (granulosa) cell-specific Ar knockout mouse model show that ARs regulate the expression of key ovarian genes through modulation of H3K27me3.

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H3K27me3 modulates aberrant transcription and apoptosis in cyclophosphamide-induced ovarian granulosa cell injury [CUT&Tag]

Project description:Chemotherapy-induced ovarian damage and infertility are significant concerns for women of childbearing age with cancer, but the underlying mechanisms are still not fully understood. Our study revealed a close association between H3K27me3 and cyclophosphamide (CTX)-induced ovarian damage, especially in granulosa cells.

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H3K27me3 modulates aberrant transcription and apoptosis in cyclophosphamide-induced ovarian granulosa cell injury

Project description:H3K27me3 modulates aberrant transcription and apoptosis in cyclophosphamide-induced ovarian granulosa cell injury

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Project description:RNA was extracted from normal human granulosa cells from IVF patients (hGC1 and hGC2 samples) and from adult-type ovarian granulosa cell tumor samples (H1, H8, H20, H23, H24, H28, H30, H33, H4, H18) as described in Jamieson et al, 2010. RNA from all samples was linearly amplified using the Whole Transcriptome Amplification kit (Sigma), starting from 300ng of RNA, and with 12 amplifications cycles. cDNA was purified on columns and sent to the Nimblegen platform for hybridization and transcriptional profiling. The FOXL2 locus was gentoyped in tumor samples, and all samples were found positive for the recurrent somatic mutation p.Cys134Trp which is present in >95% of adult-type ovarian granulosa cell tumors (Shah et al, 2009).

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Human ovarian granulosa cell methylome

Project description:We used MethylCap-seq and RRBS to profile methylomes of purified human ovarian granulosa cells. Genomic DNA methylation patterns in ovarian granulosa cells were compared between two groups of women: i) oocyte donors (n=20) who were young (age 26 ± 2.2 years) and had robust response to ovarian stimulation during assisted reproductive technology (ART) (mean number of oocytes retrieved = 25); versus ii) poor responders (n=20) who were older (age 40 ± 2.3 years) and responded poorly to ovarian stimulation during ART (oocytes retrieved ≤4 and peak estradiol level ≤ 1000 pg/ml). The first group served as healthy control. The second group represented the majority of women in their early 40s who have the natural age-related decline of ovarian functions and therefore respond poorly to ovarian stimulation during ART. We compared DNA methylomes in ovarian granulosa cells from oocyte donors versus poor responders using two approaches: MethylCap-seq for broader genomic coverage, and RRBS for absolute quantification. Due to very limited amount of materials available from each poor responder, samples containing equal amounts of granulosa cell DNA were pooled from 10 individuals in each group. A second set of experiments pooling granulosa cell DNA samples from independent donor and poor responder groups (ten individuals each) was then performed.

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