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Genome-wide analysis of high glucose and DZNep (EZH2 inhibitor) induced gene expression by mouse podocytes

ABSTRACT: Analysis of DZNep-induced gene expression changes in cultured podocytes. The hypothesis tested in the present study was that DZnep ultimately augments Txnip expression, increasing oxidative stress in podocytes. These results provide important information on the response of podocytes to histone methyltransferase inhibition and a possible mechanism for DZNep action in podocytes. Total RNA obtained from cultured podocytes subjected to 48 hours in vitro, with or without DZNep.

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Advani

PROVIDER: E-GEOD-60038 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in Diabetes.

Siddiqi Ferhan S FS Majumder Syamantak S Thai Kerri K Abdalla Moustafa M Hu Pingzhao P Advani Suzanne L SL White Kathryn E KE Bowskill Bridgit B BB Guarna Giuliana G Dos Santos Claudia C CC Connelly Kim A KA Advani Andrew A

Journal of the American Society of Nephrology : JASN 20151103 7

Epigenetic regulation of oxidative stress is emerging as a critical mediator of diabetic nephropathy. In diabetes, oxidative damage occurs when there is an imbalance between reactive oxygen species generation and enzymatic antioxidant repair. Here, we investigated the function of the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) in attenuating oxidative injury in podocytes, focusing on its regulation of the endogenous antioxidant inhibitor thioredoxin interacting protein (T ...[more]

PMID: 26534922

Similar Datasets

Genome-wide analysis of high glucose and DZNep (EZH2 inhibitor) induced gene expression by mouse podocytes

Project description:Analysis of DZNep-induced gene expression changes in cultured podocytes. The hypothesis tested in the present study was that DZnep ultimately augments Txnip expression, increasing oxidative stress in podocytes. These results provide important information on the response of podocytes to histone methyltransferase inhibition and a possible mechanism for DZNep action in podocytes.

2015-12-09 | GSE60038 | GEO

DMSO control and DZNep treated MOLM-14 cells

Project description:We demonstrated that 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, induce robust apoptosis in AML cells through increased ROS production and ER stress. We identified a core gene signature including TXNIP, a major redox control molecule which is crucial in DZNep-induced apoptosis.

2011-07-01 | GSE30315 | GEO

DMSO control and DZNep treated MOLM-14 cells

2011-07-01 | E-GEOD-30315 | biostudies-arrayexpress

Genome wide mapping of H3K27me3 in differentiated mouse podocytes

Project description:We explored H3K27me3 binding sites in the genome of differentiated, conditionally immortalized mouse podocytes. Cells were allowed to differentiate for 14 days, following thermoshifting, before treatment with either vehicle (DMSO) or the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep, 5ÂµM for 48 hours) which degrades the histone methyltransferase, EZH2 ordinarily responsible for H3K27 trimethylation (H3K27me3). DNA was immunopreciptated with an H3K27me3-specific antibody. Studying H3K27me3 modification in Mouse Podocyte

2015-12-09 | E-GEOD-69610 | biostudies-arrayexpress

Genome wide mapping of H3K27me3 in differentiated mouse podocytes

Project description:We explored H3K27me3 binding sites in the genome of differentiated, conditionally immortalized mouse podocytes. Cells were allowed to differentiate for 14 days, following thermoshifting, before treatment with either vehicle (DMSO) or the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep, 5µM for 48 hours) which degrades the histone methyltransferase, EZH2 ordinarily responsible for H3K27 trimethylation (H3K27me3). DNA was immunopreciptated with an H3K27me3-specific antibody.

2015-12-09 | GSE69610 | GEO

The effect of DZNeP-exposure on activation of hepatic stellate cells analyzed by RNA-sequencing.

Project description:DZNeP is the inhibitor of Ezh2 and paly negative roles on activation of hepatic stellate cells. We used RNA sequencing to identify the effective genes of DZNeP in rat HSCs. The primary rat HSCs was isolated and purified from SD rats, and cultured in DMEM culture medium with 20% FBS for 24 hours. Then the rat HSCs was administrated with DZNeP at 1μM concentration, or with similar volume of DMSO as negative control. 48 hour later, the cells were harvested and cell lysis was subjected to RNA-sequencing. This study identified that DZNeP regulated HSC activation through upregulating the expression of many key anti-fibrotic factors including Tgfβ signaling inhibitor: Bambi; cell cycle inhibitors: p21, Gadd45s; and immunomodulatory cytokine IL10.

2020-09-30 | GSE121736 | GEO

The S-adenosyl-homosteine hydrolase inhibitor DZNeP unspecifically affects histone methylation patterns in embryos and results in developmental aberrations

Project description:3-deazaneplanocin A (DZNeP) is a promising cancer drug affecting the methylation status of histone lysine residues. To investigate the specificity and mode of action of DZNeP, zebrafish embryos displaying high histone methyltransferase activity were cultured with DZNeP and histone methylation (H3K4me3, H3K9me3, H3K27me3) was mapped by ChIP-chip genome-wide promoter at post-MBT stage (5.3 hpf) . We used a custom 2.1M probe HD promoter array (Nimblegen) for ChIP and input DNA hybridization. Peak detection was done using MA2C with P=10e-4 as cutoff.

2014-11-21 | GSE53209 | GEO

Epigenome analysis of control and KLF4-overexpressing podocytes

Project description:Genome wide DNA methylation profiling of control (vector-transfected) and KLF4-overexpressing human podocytes (parental cell line: Saleem et al. JASN 13:630, 2002). The Illumina HumanMethylation450 Beadchip was used to obtain DNA methylation profiles. Bisulphite converted DNA samples from control (vector-transfected, n=1) and KLF4-overexpressing human podocytes (n=1) were hybridised to the Illumina HumanMethylation450 Beadchip and DNA methylation was compared.

2014-11-01 | E-GEOD-41689 | biostudies-arrayexpress

Effect of mycophenolic acid on MPC-1 murine podocytes

Project description:Mycophenolic Acid (MPA) is the active component of the immunosuppressant Mycophenolate Mofetil, a potent inhibitor of the inosine monophosphate dehydrogenase. Direct effects of MPA on podocytes remain largely unknown. In order to elucidate genes and pathways affected by the drug, cultured murine podocytes exposed to MPA were subjected to RNA sequencing (RNASeq) analysis. Untreated samples served as controls. The RNASeq of MPA treated podocytes identified 351 significantly affected genes (padj < 0.05; 130 downregulated / 221 upregulated). Gene Ontology-Term enrichment analysis outlined two major groups of terms of particular interest, namely actin associated terms and terms related to inflammatory cell death. In conclusion, MPA treatment has a substantial effect on the transcriptome of podocytes. Analysis of the sequencing data revealed several non-immune cell dependent areas in which MPA possibly has a favorable effect on podocytes.

2023-03-27 | E-MTAB-11702 | biostudies-arrayexpress

Deep RNA Sequencing of native mouse podocytes and non-podocytes glomerular cells

Project description:Purpose: Next-generation sequencing (NGS) was used to define the transcriptome of native mouse podocytes and non-podocytes glomerular cells as part of a project aiming to define the molecular fingerprint of mouse podocytes. Method: Glomeruli from 29 Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J x hNPHS2Cre mice at the age of 10 weeks were purified and a single cell solution was prepared to seperate GFP-expressing (podocytes) and GFP-negative (non-podocytes glomerular cells) cells by FACS sorting. RNA was extracted and prepared for further analysis using directional, polyA+ library preparation. An Illumina HiSeq2500 was used for a paired-end sequencing of 100 cycles . Salmon and Sleuth were used for downstream analysis. Results: A total of 100 Million reads each from podocytes and non-podocytes glomerular cells could be used for further analysis.

2019-01-01 | E-MTAB-5457 | biostudies-arrayexpress

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