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KDM6 histone demethylase inhibitor GSK-J4 induces metal and stress responses in multiple myeloma cells

ABSTRACT: KDM6 histone demethylase inhibitor GSK-J4 induces metal and stress responses in multiple myeloma cells

PROVIDER: PRJNA880340 | ENA |

REPOSITORIES: ENA

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KDM6 histone demethylase inhibitor GSK-J4 induces metal and stress responses in multiple myeloma cells [GSK-J4]

Project description:Thioneins are cysteine-rich, evolutionary conserved apoproteins that regulate divalent metal homeostasis by virtue of their metal-chelation properties resulting in the ligand-bound metallothionein state. Previous studies have demonstrated a transient upregulation (102- 103-fold) of a cluster of metallothionein genes as part of a transcriptional response to a class of histone demethylase tool compounds targeting human Fe2+ dependent ketoglutarate oxygenases KDM6A (UTX) and KDM6B (JmjD3). Exposure of multiple myeloma cells to the prototypic bioactive KDM6 inhibitor GSK-J4 induces apoptotic cell death and transcriptomic profiles that are dominated by metal and metabolic stress response signatures. We here investigate the hypothesis that the metal-chelating property of GSK-J4 provides the means for transport and intracellular release of Zn2+ leading to a metallothionein transcriptomic response signature. Live cell imaging upon myeloma cell exposure to GSK-J4 shows a transient increase of intracellular free Zn2+ concentrations upon KDM6 inhibitor treatment consistent with a model of inhibitor mediated metal transport. Comparison of KDM6 inhibitor and ZnSO4 treatments in the presence or absence of metal chelators show that both treatment conditions induce different transcription factor repertoires with an overlapping MTF1 transcriptional regulation responsible for metallothionein and metal ion transport regulation.

2022-09-16 | GSE213291 | GEO

KDM6 histone demethylase inhibitor GSK-J4 induces metal and stress responses in multiple myeloma cells [ZNSO]

2022-09-16 | GSE213292 | GEO

KDM6 histone demethylase inhibitor GSK-J4 induces metal and stress responses in multiple myeloma cells [GSK-J4]

Project description:KDM6 histone demethylase inhibitor GSK-J4 induces metal and stress responses in multiple myeloma cells [GSK-J4]

| PRJNA880344 | ENA

KDM6 histone demethylase inhibitor GSK-J4 induces metal and stress responses in multiple myeloma cells [ZNSO]

Project description:KDM6 histone demethylase inhibitor GSK-J4 induces metal and stress responses in multiple myeloma cells [ZNSO]

| PRJNA880343 | ENA

KDM6 Inhibition induces DNA Damage Response (DDR) during ESC Differentiation but not during self-renewal.

Project description:The discovery of the first histone demethylase in 2004 (LSD1/KDM1) opened new avenues for the understanding of how histone methylation impacts cellular functions. A great number of histone demethylases have been identified since, which are potentially linked to gene regulation as well as to stem cell self-renewal and differentiation. KDM6A/UTY and KDM6B/JMJD3 are both H3K27me3/2-specific histone demethylases, which are known to play a central role in regulation of posterior development, by regulating HOX gene expression. So far nothing is known about the role of histone lysine demethylases (KDMs) during early hematopoiesis. We are studying the role of KDM6A and KDM6B on self-renewal, global gene expression and on local and global chromatin states in embryonic stem cells (ESCs) and during differentiation. In order to completely abrogate KDM6 demethylase activity in ESCs we employed a specific inhibitor (GSK-J4, Kruidenier et al. 2012). Treatment of ESCs with GSK-J4 had no effect on viability and proliferation . However, ESC differentiation in the presence of GSK-J4 was completely abrogated. In conclusion we show that ESC differentiation is completely blockend in the absence of any H3K27 demethylase activity. We used microarrays to detail the global gene expression program of genes which are differentially expressed during the early differentiation of ESC derived embryoid bodies (EBs) in the presence of GSK-J4 (KDM6 Inhibitor). ESCs (R1) have been cultured and differentiated in the presence of GSK-J4 a KDM6 specific inhibitor.

2016-03-11 | E-GEOD-49886 | biostudies-arrayexpress

Jumonji Demethylase Inhibitor GSK-J4 treated Multiple Myeloma JJN3 and RPMI

Project description:Analysis of Multiple Myeloma Cell lines JJN-3 and RPMI gene expression following treated with GSK-J4 or Bortezomib Total RNA extracted from cells after 6 or 24 hour treatment with either GSK-J4, GSK-J5, Bortezomib or vehicle

2016-08-21 | E-GEOD-60600 | biostudies-arrayexpress

A novel synthetic jumonji H3K27 demethylase inhibitor GSK-J4 exert immunosuppressive activities

Project description:Using RNA-seq, we report that jumonji H3K27 demethylase inhibitor, GSK-J4, exerts potent anti-inflammatory effects on LPS-stimulated BV-2 microglial cells.

2016-09-09 | GSE79898 | GEO

Jumonji Demethylase Inhibitor GSK-J4 treated Multiple Myeloma JJN3 and RPMI

Project description:Analysis of Multiple Myeloma Cell lines JJN-3 and RPMI gene expression following treated with GSK-J4 or Bortezomib

2016-08-21 | GSE60600 | GEO

KDM6 Inhibition induces DNA Damage Response (DDR) during ESC Differentiation but not during self-renewal.

2016-03-11 | GSE49886 | GEO

Transcriptome analysis of the effects of GSK-J4 and L-ascorbic acid in female embryonic stem cells

Project description:The effects of a histone demethylase inhibitor, GSK-J4, and L-ascorbic acid for the transcriptome in female ES cells were analyzed by RNA-sequence. Total RNA was used for high-throughput sequence with Illumina HiSeq 2500 and mapped to mm10. Total RNA profile

2015-05-08 | E-GEOD-67674 | biostudies-arrayexpress

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