GEO DataSets

(Submitter supplied) The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported. A Kaplan-Meier analysis on the event free- and overall survival of NB patients indicated that the highexpression of EZH2 correlated with an unfavorable prognosis. In order to elucidate the functional roles of EZH2 in NB tumorigenesis and its aggressiveness, we knocked down EZH2 in NB cell lines using lentivirus systems. The knockdown of EZH2 significantly induced NB cell differentiation, e.g. neurite extension, and the neuronal differentiation markers, NF68 and GAP43. EZH2 inhibitors also induced NB cell differentiation. We performed a comprehensive transcriptome analysis using Human Gene Expression Microarrays and found that NTRK1 (TrkA) is one of the EZH2-related suppression targets. The depletion of NTRK1 canceled EZH2 knockdown-induced NB cell differentiation. Our integrative methylome, transcriptome, and chromatin immunoprecipitation assays using NB cell lines and clinical samples clarified that the NTRK1 P1 and P2 promoter regions were regulated differently by DNA methylation and EZH2-related histone modifications. The NTRK1 transcript variants 1/2, which were regulated by EZH2-related H3K27me3 modifications at the P1 promoter region, were strongly expressed in favorable, but not unfavorable NB. The depletion and inhibition of EZH2 successfully induced NTRK1 transcripts and functional proteins. Collectively, these results indicate that EZH2 plays important roles in preventing the differentiation of NB cells and also that EZH2-related NTRK1 transcriptional regulation may be the key pathway for NB cell differentiation.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16699

18 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

24 Samples

Download data: BW

(Submitter supplied) Purpose: Identify new targets in MYCN-amplified Neuroblastoma Methods: Kelly and LAN-1 neuroblastoma cells were treated in duplicate with 2 uM GSK126 (Excess Biosciences M60071-2) or DMSO for 2 or 5 days. RNA was extracted from cells with the RNeasy Kit (Qiagen). RNA libraries were prepared for sequencing using standard Illumina protocols. The pool of sixteen samples was sequenced on two lanes of an Illumina HiSeq, generating single end reads of 32-76 bp length. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

16 Samples

Download data: TXT

(Submitter supplied) Purpose: Identify new targets in MYCN-amplified Neuroblastoma Methods: ChIP-Seq experiments were performed on Kelly and LAN-1 neuroblastoma cells by using the following antibodies: anti-EZH2 (Cell Signaling 5246S); anti-H3K27me3 (Millipore 07-449); anti-H3K4me3 (Abcam ab8580). We evaluated the global EZH2 PRC2-dependence by identifiying direct genome-wide target genes for EZH2, H3K27me3 and H3K4me3. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

8 Samples

Download data: BW

(Submitter supplied) Background: Polycomb repressive complex 2 (PRC2) is responsible for establishing and maintaining histone H3K27 methylation during cell differentiation and proliferation. H3K27 can be mono-, di-, or tri-methylated, resulting in differential gene regulation. However, it remains unknown how PRC2 specifies the degree and biological effects of H3K27 methylation within a given cellular context. One way to determine PRC2 specificity may be through alternative splicing of Ezh2, PRC2’s catalytic subunit, during cell differentiation and tissue maturation. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

10 Samples

Download data: BED, BROADPEAK, TXT

(Submitter supplied) Investigation of EZH2 knocking down on whole genome gene expression level changes in sk-hep-1 compared to sk-hep-1-sh EZH2.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL18943

2 Samples

Download data: CALLS, PAIR

(Submitter supplied) We report the application of chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) for high-throughput profiling of H3K27me3 modifications in sk-hep-1(sk), sk-hep-1-shEZH2 (sks) and LO2 cells. Following standard ChIP procedure, 10 ng of each DNA sample was used for Illumina sequencing. Statistically significant ChIP-enriched regions (peaks) were identified by sk vs sks (p-value threshold of 10-2) or sk vs LO2 (p-value threshold of 10-3). more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

3 Samples

Download data: BED, WIG, XLS

(Submitter supplied) Post-translational modifications, such as poly(ADP-ribosyl)ation (PARylation), regulate chromatin-modifying enzymes, ultimately affecting gene expression. This study explores the role of poly(ADP-ribose) polymerase (PARP) on global gene expression in a lymphoblastoid B cell line. We found that inhibition of PARP catalytic activity with olaparib resulted in global gene deregulation, affecting approximately 11% of genes expressed. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL10999

9 Samples

Download data: TXT

(Submitter supplied) Analysis of sorted granulocyte macrophage progenitors (GMPs) in control and Bap1-deficient bone marrow cells. Loss of Bap1 in the hematopoietic compartments results in an MDS-like disease. These data allow for the examination of the genetic underpinnings of Bap1 loss in disease.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18635

6 Samples

Download data: TXT

(Submitter supplied) BAP1 and ASXL1 interact to form a polycomb deubiquitinase complex that removes monoubiquitin from histone H2A lysine 119 (H2AK119Ub). However, BAP1 and ASXL1 are mutated in distinct cancer types, consistent with independent roles in regulating epigenetic state and malignant transformation. Here we demonstrate that Bap1 loss results in increased trimethylated histone H3 lysine 27 (H3K27me3), elevated Ezh2 expression, and enhanced repression of Polycomb Repressive Complex 2 (PRC2) targets. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

11 Samples

Download data: BW

(Submitter supplied) Neuroblastoma (NB), a malignant embryonic tumor arising from primitive neural crest cells, accounts for more than 7% of malignancies and around 15% of cancer-related mortality in childhood. Better elucidating the mechanisms of tumorigenesis and aggressiveness is important for improving the therapeutic efficiencies of NB. Through mining public microarray and RNA sequencing datasets, we identified neuroblastoma highly expressed 1 (NHEG1) as a novel 1360-bp lncRNA associated with poor outcome of NB. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17586

6 Samples

Download data: CEL

(Submitter supplied) We recently found that the tetraspanin family member, CD82, which is aberrantly expressed in chemotherapy-resistant CD34+/CD38− acute myelogenous leukemia (AML) cells, negatively regulates matrix metalloproteinase 9, and plays an important role in enabling CD34+/CD38− AML cells to adhere to the bone marrow microenvironment. This study explored novel functions of CD82 that contribute to AML progression. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL14550

6 Samples

Download data: TXT

(Submitter supplied) Inhibition of H3K27 methyltransferase EZH2 enhances osteogenic commitment of human mesenchymal progenitors and Ezh2 inactivation in mouse calvarial cells induces a post-proliferative state concomitant with increased production of a bone-related mineralizing extra-cellular matrix.

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL11154 GPL13112

19 Samples

Download data: TSV

(Submitter supplied) The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

5 Samples

Download data: BW

(Submitter supplied) The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. more...

Organism:

Mus musculus

Type:

Other

Platform:

GPL19057

15 Samples

Download data: BED, BW

(Submitter supplied) The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

12 Samples

Download data: BED, BW

(Submitter supplied) The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

22 Samples

Download data: BW, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24247

10 Samples

Download data: BW

(Submitter supplied) The regulation of gene expression through histone post-translational modifications plays a crucial role in breast cancer progression. However, the molecular mechanisms underlying the contribution of histone modification to tumor initiation remain unclear. To gain a deeper understanding of the role of the histone modifier Enhancer of Zeste homology 2 (Ezh2) in the early stages of mammary tumor progression, we employed an inducible mammary organoid system bearing conditional Ezh2 alleles that faithfully recapitulates key events of Luminal B breast cancer initiation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

6 Samples

Download data: XLS

(Submitter supplied) The regulation of gene expression through histone post-translational modifications plays a crucial role in breast cancer progression. However, the molecular mechanisms underlying the contribution of histone modification to tumor initiation remain unclear. To gain a deeper understanding of the role of the histone modifier Enhancer of Zeste homology 2 (Ezh2) in the early stages of mammary tumor progression, we employed an inducible mammary organoid system bearing conditional Ezh2 alleles that faithfully recapitulates key events of Luminal B breast cancer initiation. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24247

4 Samples

Download data: BW