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Genome-wide maps of H3K79Me3 binding sites in ovarian cancer cell line OVCAR5 and expression profile of DOT1L knockdown OVCAR5 cells (RNA-seq)

ABSTRACT: This study characterized the genome-wide binding of histone 3 lysine 79 tri-methylation and expression profile of DOT1L knockdown in OVCAR5 cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199472 | GEO | 2022/11/08

REPOSITORIES: GEO

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Genome-wide maps of H3K79Me3 binding sites in ovarian cancer cell line OVCAR5 and expression profile of DOT1L knockdown OVCAR5 cells (ChIP-seq)

Project description:This study characterized the genome-wide binding of histone 3 lysine 79 tri-methylation and expression profile of DOT1L knockdown in OVCAR5 cells.

2022-11-08 | GSE199473 | GEO

Genome-wide maps of H3K79Me3 binding sites in ovarian cancer cell line OVCAR5 and expression profile of DOT1L knockdown OVCAR5 cells

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

2022-11-08 | GSE199474 | GEO

Genome-wide maps of FOXK2 binding sites in ovarian cancer cell line OVCAR5 and expression profile of FOXK2 knockdown OVCAR5 cells (RNA-seq)

Project description:This study characterized the genome-wide binding of FOXK2 in ovarian cancer (OC) cell OVCAR-5 and investigated the expression profile of OVCAR5 cells with FOXK2 knocking-down.

2022-05-18 | GSE173779 | GEO

Genome-wide maps of FOXK2 binding sites in ovarian cancer cell line OVCAR5 and expression profile of FOXK2 knockdown OVCAR5 cells (ChIP-seq)

Project description:This study characterized the genome-wide binding of FOXK2 in ovarian cancer (OC) cell OVCAR-5 and investigated the expression profile of OVCAR5 cells with FOXK2 knocking-down.

2022-05-18 | GSE173777 | GEO

DOT1L regulates pericentromeric heterochromatin

Project description:Many repetitive DNA elements are packaged in heterochromatin, but depend on occasional transcription to maintain long-term silencing. The factors that promote transcription of repeat elements in heterochromatin are largely unknown. Here, we show that DOT1L, a histone methyltransferase that modifies lysine 79 of histone H3 (H3K79), is required for transcription of major satellite repeats to maintain pericentromeric heterochromatin (PCH), and that this function is essential for preimplantation development. DOT1L is a transcriptional activator at single-copy genes but does not have a known role in repeat element transcription. We show that H3K79me3 is specifically enriched at repetitive elements, that loss of DOT1L compromises pericentromeric major satellite transcription, and that this function depends on interaction between DOT1L and the chromatin remodeler SMARCA5. DOT1L inhibition causes chromosome breaks and cell cycle defects, and leads to embryonic lethality. Together, our findings uncover a vital new role for DOT1L in transcriptional activation of heterochromatic repeats.

2023-05-26 | PXD028824 | Pride

Characterization of resistance to prexasertib in ovarian cancer cell line OVCAR5

Project description:We developed a CHK1 inhibitor Prexasertib resistant strain of ovarian cancer cell line OVCAR5 in lab. This was used to compare transcriptome profiles to study changes in expression profiles of genes that might be involved with resistance. Total RNA was isolated from three replicate cultures of OVCAR5R (IC50 viability >3 micromolar Prexasertib) and 3 replicate cultures of parental OVCAR5 (IC50 viability=7.5nM) and then subjected to Hiseq4000 illumina RNA-seq analysis, with paired end sequencing. Data file contains CPM-TMM values after zoom normalization.

2020-05-02 | GSE149724 | GEO

Genome-wide maps of FOXK2 binding sites in ovarian cancer cell line OVCAR5 and expression profile of FOXK2 knockdown OVCAR5 cells

Project description:Genome-wide maps of FOXK2 binding sites in ovarian cancer cell line OVCAR5 and expression profile of FOXK2 knockdown OVCAR5 cells

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Functional effect of DOT1L pharmacological inhibition in ERα-positive Ovarian Cancer cells

Project description:Estrogen Receptor alpha (ERα), a nuclear receptor with transcriptional activity, is a master regulator of estrogen signaling, widely known as therapeutic target in hormone-responsive breast cancer (BC). Moreover, ERα is highly expressed in approximately 80% of High Grade Serous Ovarian Cancer (HGSOC), the most common epithelial ovarian carcinoma. Despite some promising clinical trials evaluating endocrine therapy in this type of tumor, the role of ERα is still unknown. Epigenetic changes, such as DNA methylation, are emerging as key contributing factors to carcinogenesis. Disruptor of telomeric silencing-1-like (DOT1L), the only known histone methyl transferase capable to produce H3K79 mono, di and tri-methylation, modulates ERα actions in hormone-responsive BC. Considering this evidence, ERα-DOT1L association was confirmed in ERα-positive OC cells, PEO1 and PEO4, by Co-IP. DOT1L pharmacological inhibition by EPZ004777 (EPZ) revealed the involvement of this epigenetic enzyme in cell proliferation, cell cycle progression and apoptosis. Transcriptome profiling after ICI (a Selective Estrogen Receptor Degrader) and EPZ treatment, in both cell lines, has underlined a deep impact of both compounds on ERα-modulated genes, including the down-regulation of ERα itself. On the other hand, functional analysis showed that commonly affected transcripts are involved in different cellular processes, such as cancer cell survival, chemoresistance and cell cycle progression. Moreover, ChIP-qPCR performed on ERα promoter highlighted ERα and DOT1L co-localization, both in PEO1 and in PEO4 cells, which was reduced after EPZ treatment, suggesting a role of this complex on receptor transcriptional activity. In addition, drug combination studies performed with EPZ and ICI showed an additive effect in cell growth inhibition. Taken together, these results suggest DOT1L as a potential therapeutic target in the treatment of OC.

2019-11-04 | E-MTAB-8198 | biostudies-arrayexpress

Genome-wide maps of chromatin state of H3K79me2 in embryonic and neonatal cardiomyocytes of XMlc2-Cre;Dot1L mutants and controls

Project description:Epigenetic enzymes play critical roles in embryogenesis by defining higher-order chromatin structures required for the establishment of organ-specific transcriptional networks. In this study we investigated the role of the histone 3 lysine 79 methyltrasferase Dot1L in cardiomyocytes during development. We conducted chromatin immunoprecipitation experiments for H3K79me2 in embryonic (E16.5) and neonatal (P1) cardiomyocytes from Dot1L cardiomyocyte-specific conditional knock out and control mice. Genes that bear this modification in DOT1L controls lose it in cKOs, consistent with the model of DOT1L as the sole histone K79 methyltransferase. Overall, we identified enrichment of methylation of H3K79 in gene bodies and in regulatory regions associated wih trascription factors essential for cardiac patterning at E16.5 and with genes important for cardiomyocyte proliferation and maturation in the postnatal period.

2022-11-11 | GSE184109 | GEO

Genome-wide maps of FOXK2 binding sites in ovarian cancer cell line OVCAR5 and expression profile of FOXK2 knockdown OVCAR5 cells (ChIP-seq)

Project description:Genome-wide maps of FOXK2 binding sites in ovarian cancer cell line OVCAR5 and expression profile of FOXK2 knockdown OVCAR5 cells (ChIP-seq)

| PRJNA727006 | ENA

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