Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

KDM5 histone demethylases repress innate immune response via suppression of STING

ABSTRACT: KDM5 histone demethylases repress innate immune response via suppression of STING

PROVIDER: PRJNA427473 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6417891.fastq.gz	Fastqsanger.gz
	SRR6417892.fastq.gz	Fastqsanger.gz
	SRR6417893.fastq.gz	Fastqsanger.gz
	SRR6417894.fastq.gz	Fastqsanger.gz
	SRR6417895.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

KDM5 histone demethylases repress innate immune response via suppression of STING

Project description:Tri-methylation on histone H3 lysine 4 (H3K4me3) is enriched near transcription start sites and correlates with active transcription. Like other histone marks, methylation on H3K4 is catalyzed by the respective methyltransferases and erased by demethylases. Lysine demethylase 5 (KDM5) family of Fe (II) and α-ketoglutarate-dependent dioxygenases removes the methyl groups from H3K4me3. All four family members of KDM5 demethylases (KDM5A-D) share sequence identity, have similar in vitro kinetic parameters, and display functional redundancy. To determine the effects of complete depletion of KDM5 activity, we treated MCF7 cells with DMSO, or two pan-KDM5 specific inhibitors, KDM5-C70 (our lab code 443) and CPI-48 (our lab code 278) and performed RNA sequencing to determine gene expression changes after KDM5 inhibitor treatment.

2018-07-03 | GSE108502 | GEO

KDM5 histone demethylases repress immune response via suppression of STING.

Project description:Cyclic GMP-AMP (cGAMP) synthase (cGAS) stimulator of interferon genes (STING) senses pathogen-derived or abnormal self-DNA in the cytosol and triggers an innate immune defense against microbial infection and cancer. STING agonists induce both innate and adaptive immune responses and are a new class of cancer immunotherapy agents tested in multiple clinical trials. However, STING is commonly silenced in cancer cells via unclear mechanisms, limiting the application of these agonists. Here, we report that the expression of STING is epigenetically suppressed by the histone H3K4 lysine demethylases KDM5B and KDM5C and is activated by the opposing H3K4 methyltransferases. The induction of STING expression by KDM5 blockade triggered a robust interferon response in a cytosolic DNA-dependent manner in breast cancer cells. This response resulted in resistance to infection by DNA and RNA viruses. In human tumors, KDM5B expression is inversely associated with STING expression in multiple cancer types, with the level of intratumoral CD8+ T cells, and with patient survival in cancers with a high level of cytosolic DNA, such as human papilloma virus (HPV)-positive head and neck cancer. These results demonstrate a novel epigenetic regulatory pathway of immune response and suggest that KDM5 demethylases are potential targets for antipathogen treatment and anticancer immunotherapy.

| S-EPMC6095604 | biostudies-literature

H3K4me3 ChIP in multiple myeloma MM1S cells in the presence and absence of KDM5-C70

Project description:In this experiment we demonstrate the use of an inhibitor of the KDM5 family of histone demethylases, KDM5-C70, on H3K4me3 marks in the multiple myeloma cell line MM1S. KDM5-C70 increases H3K4me3 in a global fashion across the genome. Examination of H3K4me3 mark across MM1S cells treated with either KDM5-C70 or vehicle control

2016-04-05 | E-GEOD-78206 | biostudies-arrayexpress

Effect of KDM5 histone demethylase in 3T3-L1 differentiation

Project description:The KDM5 histone demethylases regulate histone methylation to modulate chromatin structure and gene expression. Using a KDM5 enzyme inhibitor (KDM5-C70) and transcriptome profiling by RNA-sequencing in 3T3-L1 cells at different states of differentiation, we determined that KDM5 activity influences the induction of genes associated with cell cycle regulation and mitochondrial function.

2024-03-04 | GSE239950 | GEO

KDM5 Lysine Demethylases Are Involved in Maintenance of 3'UTR Length

Project description:KDM5 Lysine Demethylases Are Involved in Maintenance of 3'UTR Length

| PRJNA279265 | ENA

Sex specific role of KDM5 demethylases in Alcohol-associated Liver Disease

Project description:Sex specific role of KDM5 demethylases in Alcohol-associated Liver Disease

| PRJNA802555 | ENA

H3K4me3 ChIP in multiple myeloma MM1S cells in the presence and absence of KDM5-C70

2016-04-05 | GSE78206 | GEO

Sex specific role of KDM5 demethylases in Alcohol-associated Liver Disease

Project description:Alcohol-associated liver disease (ALD) is a major cause of alcohol related mortality. The specific mechanisms responsible for ALD development and progression are not fully understood, and there is limited therapy for any stage of ALD. Sex differences are often disregarded in in genetic and mechanistic studies. We aimed to take an unbiased approach to define sex specific pathways in livers exposed to alcohol. METHODS: Mice were fed LieberDeCarli alcohol liquid diet for 3 weeks. To identify the role of Kdm5b and Kdm5c we injected mice with AAV-shControl at 2x10^11 gc per mouse or AAV-shKdm5b and AAV-Kdm5c vectors at 10^11 gc per mouse. To assess the role of AhR we injected mice with AAV-shControl or AAV-shAhR vectors at 10^11 gc per mouse. RESULTS: We found several pathways affected by alcohol in sex specific way and identified KDM5 demethylases as contributors to that specificity.

2022-02-08 | GSE195889 | GEO

RNA-seq of HER2-positive breast cancer BT474 cell line in response to KDM5 ihibition

Project description:Alterations in the histone methylation profiles are observed in various types of cancer and targeting of this epigenetic process has therapeutic potential. Here we provide proof-of-principle that pharmacological targeting of KDM5 histone-demethylases is a new strategy for the personalized treatment of HER2-positive breast cancer. This analysis demonstrates that cells characterized by HER2-positivity are particularly sensitive to KDM5 inhibition. The results are confirmed in an appropriate in vivo model with a close structural analogue (KDM5-inh1A). In selected HER2-positive breast cancer cells, we demonstrate synergistic interactions between KDM5-inh1 and HER2-targeting agents (trastuzumab and lapatinib). In addition, HER2-positive cell lines showing innate/acquired resistance to trastuzumab show sensitivity to KDM5-inh1. The levels of KDM5A/B/C proteins, which are selectively targeted by the agent, have no significant association with KDM5-inh1 responsiveness across our panel of breast cancer cell lines, suggesting the existence of other determinants of sensitivity. Using RNA-sequencing data of the breast cancer cell lines, we generate a gene-expression model, consisting of fifteen genes, which is a robust predictor of KDM5-inh1 sensitivity. In a test set of breast cancers, this model correctly predicts sensitivity to the compound in a large fraction of HER2+ tumors. In conclusion, KDM5 inhibition has potential in the treatment of HER2+ breast cancer and our gene-expression model can be developed into a diagnostic tool to select patients who may benefit from treatments based on KDM5-inhibitors.

2019-02-01 | E-MTAB-7433 | biostudies-arrayexpress

KDM5 Lysine Demethylases Are Involved in Maintenance of 3'UTR Length [ChIP-Seq]

Project description:We discovered that the Saccharomyces cerevisiae lysine demethylase, Jhd2 (also known as KDM5), recruits 3'UTR processing machinery and promotes alteration of 3'UTR length in a demethylase-dependent manner. Interaction of Jhd2 with both chromatin and RNA suggests that Jhd2 affects selection of polyadenylation sites through a transcription-coupled mechanism. Wild-type yeast or yeast with JHD2 deleted were grown to mid-log phase. ChIP analysis performed for H3K4me3, Pol2, IgG.

2016-03-23 | E-GEOD-67211 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data