Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HDAC6 regulates NF-κB signalling by HDAC-dependent and independent mechanisms to control chondrocyte IL-1-induced MMP and inflammatory gene expression [HDAC siRNA exp]

ABSTRACT: Analysis of the effect of HDAC6 knockdown on IL-1-induced gene expression in SW1353 chondrocytes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186688 | GEO | 2021/10/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

HDAC6 regulates NF-κB signalling by HDAC-dependent and independent mechanisms to control chondrocyte IL-1-induced MMP and inflammatory gene expression [TSA exp]

Project description:Analysis of the effect of HDAC inhibitor TSA on IL-1-induced gene expression in SW1353 chondrocytes.

2021-10-29 | GSE186689 | GEO

HDAC6 regulates NF-κB signalling to control chondrocyte IL-1-induced MMP and inflammatory gene expression.

Project description:Elevated pro-inflammatory signalling coupled with catabolic metalloproteinase expression is a common feature of arthritis, leading to cartilage damage, deterioration of the joint architecture and the associated pain and immobility. Countering these processes, histone deacetylase inhibitors (HDACi) have been shown to suppress matrix metalloproteinase (MMP) expression, block cytokine-induced signalling and reduce the cartilage degradation in animal models of the arthritis. In order to establish which specific HDACs account for these chondro-protective effects an HDAC1-11 RNAi screen was performed. HDAC6 was required for both the interleukin (IL)-1 induction of MMP expression and pro-inflammatory interleukin expression in chondrocytes, implicating an effect on NF-κB signalling. Depletion of HDAC6 post-transcriptionally up-regulated inhibitor of κB (IκB), prevented the nuclear translocation of NF-κB subunits and down-regulated NF-κB reporter activation. The pharmacological inhibition of HDAC6 reduced MMP expression in chondrocytes and cartilage collagen release. This work highlights the important role of HDAC6 in pro-inflammatory signalling and metalloproteinase gene expression, and identifies a part for HDAC6 in the NF-κB signalling pathway. By confirming the protection of cartilage this work supports the inhibition of HDAC6 as a possible therapeutic strategy in arthritis.

| S-EPMC9033835 | biostudies-literature

HDAC6 regulates NF-κB signalling by HDAC-dependent and independent mechanisms to control chondrocyte IL-1-induced MMP and inflammatory gene expression

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

2021-10-29 | GSE186690 | GEO

HDAC6 regulates NF-κB signalling by HDAC-dependent and independent mechanisms to control chondrocyte IL-1-induced MMP and inflammatory gene expression [HDAC siRNA exp]

Project description:HDAC6 regulates NF-κB signalling by HDAC-dependent and independent mechanisms to control chondrocyte IL-1-induced MMP and inflammatory gene expression [HDAC siRNA exp]

| PRJNA775079 | ENA

HDAC6 regulates NF-κB signalling by HDAC-dependent and independent mechanisms to control chondrocyte IL-1-induced MMP and inflammatory gene expression [TSA exp]

Project description:HDAC6 regulates NF-κB signalling by HDAC-dependent and independent mechanisms to control chondrocyte IL-1-induced MMP and inflammatory gene expression [TSA exp]

| PRJNA775078 | ENA

HDAC6 regulates NF-κB signalling by HDAC-dependent and independent mechanisms to control chondrocyte IL-1-induced MMP and inflammatory gene expression

Project description:HDAC6 regulates NF-κB signalling by HDAC-dependent and independent mechanisms to control chondrocyte IL-1-induced MMP and inflammatory gene expression

| PRJNA775073 | ENA

Hdac6 regulates Tip60-p400 function in stem cells (sequencing)

Project description:The Tip60 (also known as Kat5) lysine acetyltransferase functions broadly as a transcriptional co-activator that acetylates histones. In contrast, Tip60 functions in embryonic stem cells (ESCs) both to silence genes that promote differentiation and to activate genes required for proliferation. The mechanism by which Tip60 functions as a repressor is unknown. Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60-p400 complex from ESCs and is necessary for complete silencing of most differentiation genes targeted by Tip60. In contrast to differentiated cells, where Hdac6 is mainly cytoplasmic and does not interact with Tip60, Hdac6 is largely nuclear in ESCs and neural stem cells (NSCs) and interacts with Tip60-p400 in both cell types. Hdac6 is enriched at promoters bound by Tip60-p400 in ESCs, but while Tip60 binds on both sides of transcription start sites (TSSs), Hdac6 binding overlaps with only the downstream Tip60 peak. Surprisingly, Hdac6 does not deacetylate histones at these sites, but rather is required for Tip60 binding. These data suggest that nuclear exclusion of Hdac6 during differentiation plays a major role in modulation of Tip60-p400 function. We determined the genome-wide localization of Tip60 and Hdac6 in mouse ES cells, and examined genomic binding profiles of Tip60 and Hdac6 upon indicated knockdown by ChIP-seq. We examined genomic binding profiles of p400 upon indicated knockdown by ChIP-seq.

2013-11-20 | E-GEOD-42209 | biostudies-arrayexpress

Transcriptomic analysis of HDAC6-selective and broad HDAC inhibitors in human WT iPSC cardiomyocytes

Project description:Dilated cardiomyopathy (DCM) is characterized by reduced cardiac output, as well as thinning and enlargement of left ventricular chambers. These characteristics eventually lead to heart failure. Current standards of care do not target the underlying molecular mechanisms associated with genetic forms of heart failure, driving a need to develop novel therapeutics for DCM. To identify candidate therapeutics, we developed an in vitro DCM model using induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) deficient in BCL2-associated athanogene 3 (BAG3). With these BAG3-deficient iPSC-CMs, we identified cardioprotective drugs with a phenotypic screen and deep learning. Using a library of 5500 bioactive compounds and siRNA validation, we identified that inhibiting histone deacetylase 6 (HDAC6) was cardioprotective at the sarcomere level. We translated this finding to a BAG3 cardiac-knockout (BAG3cKO) mouse model of DCM, showing that inhibiting HDAC6 with two isoform-selective inhibitors (tubastatin A and a novel inhibitor TYA-018) protected heart function. In BAG3cKO and BAG3 E455K mice, HDAC6 inhibitors improved left ventricular ejection fraction and reduced left ventricular diameter at diastole and systole. We also found that HDAC6 inhibitors protected the microtubule network from mechanical damage, increased autophagic flux, decreased apoptosis, and reduced inflammation in the heart. Our results demonstrate the power of combining iPSC-CMs with phenotypic screening and deep learning to accelerate target and drug discovery, and they support the development of novel therapies that address underlying mechanisms associated with heart disease.

2021-12-31 | GSE180248 | GEO

HDAC6 Inhibition Disrupts HDAC6-P300 Interaction Reshaping the Cancer Chromatin Landscape (ChIP-Seq)

Project description:Histone deacetylases (HDACs) are crucial regulators of gene expression, DNA synthesis, and cellular processes, making them essential targets in cancer research. HDAC6, specifically, influences protein stability and chromatin dynamics. Despite HDAC6's potential therapeutic value, its exact role in gene regulation and chromatin remodeling needs further clarification. This study examines how HDAC6 inactivation influences lysine acetyltransferase P300 stabilization and subsequent effects on chromatin structure and function in cancer cells. We employed the HDAC6 inhibitor ITF3756, siRNA, or CRISPR/Cas9 gene editing to inactivate HDAC6 in different epigenomic backgrounds. Constantly, this inactivation led to significant changes in chromatin accessibility, particularly increased acetylation of histone H3 lysines 9, 14, and 27 (ATAC-seq and H3K27Ac ChIP-seq analysis). Transcriptomics, proteomics, and gene ontology analysis revealed gene changes in cell proliferation, adhesion, migration, and apoptosis. Significantly, HDAC6 inactivation altered P300 ubiquitination, stabilizing P300 and leading to downregulating genes critical for cancer cell survival. Our study highlights the substantial impact of HDAC6 inactivation on the chromatin landscape of cancer cells and suggests a role for P300 in contributing to the anticancer effects. The stabilization of P300 with HDAC6 inhibition proposes a potential shift in therapeutic focus from HDAC6 itself to its interaction with P300. This finding opens new avenues for developing targeted cancer therapies, improving our understanding of epigenetic mechanisms in cancer cells.

2024-08-19 | GSE273645 | GEO

HDAC6 Inhibition Disrupts HDAC6-P300 Interaction Reshaping the Cancer Chromatin Landscape (ATAC-Seq)

2024-08-19 | GSE273644 | GEO