Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE44868 | GEO | 2013/07/09

SECONDARY ACCESSION(S): PRJNA192435

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition.

Project description:Histone deacetylase inhibitors (HDACis) have been shown to potentiate hippocampal-dependent memory and synaptic plasticity and to ameliorate cognitive deficits and degeneration in animal models for different neuropsychiatric conditions. However, the impact of these drugs on hippocampal histone acetylation and gene expression profiles at the genomic level, and the molecular mechanisms that underlie their specificity and beneficial effects in neural tissue, remains obscure. Here, we mapped four relevant histone marks (H3K4me3, AcH3K9,14, AcH4K12 and pan-AcH2B) in hippocampal chromatin and investigated at the whole-genome level the impact of HDAC inhibition on acetylation profiles and basal and activity-driven gene expression. HDAC inhibition caused a dramatic histone hyperacetylation that was largely restricted to active loci pre-marked with H3K4me3 and AcH3K9,14. In addition, the comparison of Chromatin immunoprecipitation sequencing and gene expression profiles indicated that Trichostatin A-induced histone hyperacetylation, like histone hypoacetylation induced by histone acetyltransferase deficiency, had a modest impact on hippocampal gene expression and did not affect the transient transcriptional response to novelty exposure. However, HDAC inhibition caused the rapid induction of a homeostatic gene program related to chromatin deacetylation. These results illuminate both the relationship between hippocampal gene expression and histone acetylation and the mechanism of action of these important neuropsychiatric drugs.

| S-EPMC3783173 | biostudies-literature

Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-07-09 | E-GEOD-44868 | biostudies-arrayexpress

Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition

Project description:Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition

| PRJNA192435 | ENA

Aberrant chromatin acetylation in MLL-AF9 leukemia mediates the response to HDAC inhibition

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-03-01 | E-GEOD-54348 | biostudies-arrayexpress

Vascular histone deacetylation by pharmacological HDAC inhibition

Project description:This SuperSeries is composed of the SubSeries listed below. HDAC inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone proteins. Often studied at single loci, increased histone acetylation is the paradigmatic mechanism of action, however, little is known of the extent of genome-wide changes of the mammalian genome when stimulated by the hydroxamic acids, TSA and SAHA. In primary human vascular endothelial cells we map the chromatin modifications, histone H3 acetylation of lysine 9 and 14 (H3K9/14ac) using chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq). Since acetylation mediated gene expression is often associated with modification of other lysine residues we also examined H3K4me3 and H3K9me3 as well as changes in CpG methylation (CpG-seq). Genome-wide mRNA sequencing indicates the differential expression of about 30% of genes, with almost equal numbers being up- and down- regulated. We observe deacetylation conferred by TSA and SAHA that are associated with decreased gene expression. Histone deacetylation is associated with the loss of p300/CBP binding at gene promoters. This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation. Refer to individual Series

2014-02-23 | E-GEOD-37378 | biostudies-arrayexpress

Aberrant chromatin acetylation in MLL-AF9 leukemia mediates the response to HDAC inhibition

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

2015-03-01 | GSE54348 | GEO

Epigenetic and metabolic reprogramming by HDAC inhibition targets NRF2-active tumors

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

2023-03-30 | GSE220839 | GEO

HDAC inhibition results in widespread alteration of the histone acetylation landscape and BRD4 targeting to gene bodies.

Project description:Histone acetylation levels are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) that antagonistically control the overall balance of this post-translational modification. HDAC inhibitors (HDACi) are potent agents that disrupt this balance and are used clinically to treat diseases including cancer. Despite their use, little is known about their effects on chromatin regulators, particularly those that signal through lysine acetylation. We apply quantitative genomic and proteomic approaches to demonstrate that HDACi robustly increases a low-abundance histone 4 polyacetylation state, which serves as a preferred binding substrate for several bromodomain-containing proteins, including BRD4. Increased H4 polyacetylation occurs in transcribed genes and correlates with the targeting of BRD4. Collectively, these results suggest that HDAC inhibition functions, at least in part, through expansion of a rare histone acetylation state, which then retargets lysine-acetyl readers associated with changes in gene expression, partially mimicking the effect of bromodomain inhibition.

| S-EPMC7886050 | biostudies-literature

Dual Roles of Histone H3 Lysine 9 Acetylation in Human Embryonic Stem Cell Pluripotency and Neural Differentiation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-03-11 | E-GEOD-66779 | biostudies-arrayexpress

Pharmacological HDAC inhibition attenuates cardiac hypertrophy and histone acetylation of target genes

Project description:Cardiac hypertrophy is characterized by an increase in heart size and profound gene expression changes. Pharmacological histone deacetylase (HDAC) inhibitors attenuate pathological cardiac remodeling and hypertrophic gene expression. Published literature has linked enzymes that mediates histone acetylation to pathogenesis, however, the role of histone acetylation to define hypertrophic gene regulatory events are not well understood. We used chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (seq) to comprehensively examine genome-wide histone acetylation changes in a pre-clinical model of pathological cardiac hypertrophy by transverse aortic constricted (TAC). We examined the gene targets conferred by the prototypical HDAC inhibitor Trichostatin A (TSA). TSA induces genome-wide histone acetylation and deacetylation in the heart. Alterations to histone acetylation were found on genes involved in cardiac morphology such as cardiac contraction, collagen deposition, inflammation and extracellular matrix. Gene set enrichment analysis identified NF-kappa B (NFKB), as a transcription factor positively correlated with TAC and negatively correlated with TSA by ChIP-seq. Histone acetylation on the promoters of NKFB target genes was increased, consistent with gene activation. In contrast, the promoters of these genes were deacetylated by TSA in hypertrophic animals and reduced expression of NFKB target genes. Our results suggest a potential mechanism for TSA mediated cardioprotection conferred by histone deacetylation of target genes implicating the importance of inflammation. ChIP-seq profiles for histone acetylation in left ventricles of mice that develop cardiac hypertrophy and treated with HDAC inhibitors were generated by deep sequencing, using Illumina GAIIx.

2015-04-25 | E-GEOD-63590 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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