Histone Deacetylase Inhibition Promotes Osteoblast Maturation by Altering the Histone 4 (H4) Epigenome (ChIP-Seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Jennifer Westendorf
PROVIDER: E-GEOD-50551 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Suberoylanilidehydroxamic acid (SAHA) significantly increased the expression levels of 127 transcripts and suppressed expression of 130 genes by more than 2-fold within 3 standard deviations of the mean in differentiating MC3T3 sc4 osteoblasts Total RNA was obtained from differentiating MC3T3 sc4 cells treated with SAHA or vehicle (DMSO).
2013-09-04 | E-GEOD-50549 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-09-04 | E-GEOD-50552 | biostudies-arrayexpress
Project description:Balance between histone acetylation and deacetylation is fundamental for proper gene function, thus knowledge of how to modulate these epigenetic processes is important for understanding of nuclear events, including replication, transcription, splicing and DNA repair. Here, we have studied an effect of HDAC inhibitor, SAHA, and we compared it with an effect of natural product, derivative of anacardic acid (MG149). Recently, it was discovered that MG149 has inhibitory potential for HATs' activity on histone H3 and H4 when tested on nuclear extracts.
2014-01-20 | E-MTAB-1481 | biostudies-arrayexpress
Project description:Dendritic cells (DC) play a vital role in the induction of activation or tolerance of immune response. STAT3 is a master transcriptional regulator of immune response in DCs by positively or negatively regulating DC function, but the mechanisms are unknown. STAT3 is post-translationally modified by acetylation or phosphorylation. While much is understood about transcriptional targets of phosphorylated STAT3, the gene targets and the functional impact of acetylated-STAT3 remain unclear. We aimed to answer the gene targets of acetylated-STAT3 and test the hypothesis that acetylation of STAT3 plays a key role in negative regulation of DCs. We performed genome-wide binding analysis of acetyl-STAT3 by ChIP-Seq coupled with gene expression microarrays. Acetylation of STAT3 induced by SAHA increased its capability to bind to target DNA sites in genome. Theses binding sites were mostly proximal but some were also distal up to over 100 kb from transcription start site. Gene expression array showed 1701 genes up-regulated and 1668 genes down-regulated. Proximal binding of acety-STAT3 showed more effective transcription function than distal binding. In top 500 binding peaks, the frequency of canonical motifs bound by acetyl-STAT3 were significantly higher than that for noncanonical motifs (p<0.00001). Functional analysis revealed that acetyl-STAT3 regulates target genes by upregulating genes that are primarily involved in negative regulation of cytokine production and IL-10 signaling, or downregulating genes that are primarily involved in immune effector process and antigen processing/presentation. Upregulation of IL-10Ra by acetyl-STAT3 contributes to the enhanced sensitivity of IL-10 signaling and negative regulation of DC function. Bone marrow derived dendritic cells were treated with SAHA (500 nm) or diluent for 12 hours. ChIP was performed using antibodies against STAT3, H3K4me3 and matched IgG control. DNA binding profiles were generated by deep sequencing using Illumina HiSeq 2000.
2015-11-05 | E-GEOD-74262 | biostudies-arrayexpress
Project description: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. HAEC mRNA profiles of SAHA treated and control samples were generated by deep sequencing, in triplicate, using Illumina GAIIx.
2014-02-23 | E-GEOD-54912 | biostudies-arrayexpress
Project description:Artificial epigenetic switches are of increasing demand owing to the critical role of the dynamic epigenome in orchestrating genome-wide transcriptional activation. Recently, we divulged that certain epigenetically active small molecules called SAHA-PIPs containing the cell permeable pyrrole-imidazole polyamides (PIPs) as DNA recognition module and a histone deacetylases inhibitor SAHA as functional module, is capable of triggering targeted transcriptional activation of pluripotency and germ cell genes in mouse and human fibroblasts, respectively. Through microarray studies and functional analysis, here we demonstrate the first ever example about the remarkable ability of 32 different SAHA-PIPs to trigger transcriptional activation of their own unique set of genes and noncoding RNAs. QRT-PCR studies validated that certain SAHA-PIPs could induce several therapeutically important genes including KSR2 and SEMA6A to suggest its potential use as reagents capable of targeted transcriptional activation and as probe(s) to identify the functional relevance of the uncharacterized genes. Gene induction by a SAHA-PIP and SAHA was measured after treating human dermal fibroblasts at 48 h time-point. Experiment includes a vehicle (DMSO) treatment as a negative control.
2013-12-31 | E-GEOD-53316 | biostudies-arrayexpress
Project description:Suberoylanilide hydroxamic acid (SAHA) has been assessed in clinical trials as part of a “shock and kill” strategy to cure HIV-infected patients. While it was effective at inducing expression of HIV RNA "shock" , treatment with SAHA did not result in the reduction of reservoir size "kill". We therefore utilized a systems biology approach to dissect the mechanisms of action of SAHA that may explain its limited success in “shock and kill” strategies. CD4+ T cells from HIV seronegative donors were treated with 1 uM SAHA or its solvent dimethyl sulfoxide for 24 hours. Differential protein expression and post-translational modification was measured with two-dimensional liquid chromatography - tandem mass spectrometry iTRAQ proteomics. Gene expression changes were assessed by Illumina microarrays. Using limma package in the R computing environment, we identified 185 proteins, 18 phosphorylated forms, 4 acetylated forms and 2,982 genes, whose expression was modulated by SAHA. A protein interaction network integrating these 4 data types identified the transcriptional regulator HMGA1 to be upregulated by SAHA at the transcript, protein and acetylated protein levels. HMGA1 has been shown to repress HIV transcription, which is not optimal with respect to a shock and kill strategy. Further functional category assessment of proteins and genes modulated by SAHA identified gene ontology terms related to NFB signaling, protein folding and autophagy, which are all relevant to HIV reactivation. In summary, this study identified a number of host factors that may be therapeutically targeted to achieve more potent HIV reactivation in the “shock and kill” treatment, when using SAHA, either through modification of SAHA itself or through combination with other latency reversing agents. Finally, proteome profiling highlighted a number of potential adverse effects of SAHA, which transcriptome profiling alone would not have identified.
2015-09-10 | PXD002150 | Pride
Project description: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. HAEC ChIP-seq profiles for 3 histone marks of SAHA treated and control samples were generated by deep sequencing, in triplicate, using Illumina GAIIx.
2014-02-23 | E-GEOD-54909 | biostudies-arrayexpress
Project description:ChIP-Seq analysis revealed that suberoylanilidehydroxamic acid (SAHA) increases genome-wide H4 acetylation in differentially regulated genes, except for the 500 bp upstream of transcription start sites (TSS).
2013-09-04 | GSE50551 | GEO
Project description:Heart Failure with preserved Ejection Fraction (HFpEF) is a major global health problem but there are no effective therapies. The aim of this study was to assess the effects of histone deacetylase (HDAC) inhibition on cardiopulmonary structure, function, and metabolism in a large mammalian (feline) pressure overload model with HFpEF features. Male domestic short hair cats (n=26, aged 2mo), underwent either a sham procedure (n=5) or aortic constriction (n=21) using a pre-shaped band, resulting in slow-progressive pressure overload during subsequent growth. Two-months post-banding, banded cats were treated daily with either 10mg/kg suberoylanilide hydroxamic acid (b+SAHA) (n=8), an FDA approved pan-HDAC inhibitor, or vehicle (b+veh) (n=8) for 2 months. Echocardiography at 4-months post-banding revealed that b+SAHA animals had a significant reduction in left ventricular hypertrophy (LVH) and LA size vs b+veh animals. Invasively measured left ventricular end-diastolic pressure (LVEDP) and mean pulmonary arterial pressure (mPAP) were significantly elevated in b+veh and significantly reduced by b+SAHA. SAHA speeded ex-vivo myofibril relaxation independent of LVH and this effect correlated with in-vivo indices of LV relaxation. Furthermore, SAHA preserved lung structure, improved lung compliance and oxygenation, reflected by a decrease in alveolar-capillary wall thickness, alveolar-arterial oxygen gradient (A-aDO2), and intrapulmonary shunt. SAHA also reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar-capillary stress failure. Acetylation proteomics revealed that SAHA altered protein acetylation in cat hearts, including histones, many mitochondrial metabolic enzymes involved in electron transport chain, TCA cycle, malate aspartate shuttle and beta oxidation, as well as cytoskeletal proteins important for muscle function. These results suggest that acetylation defects in hypertrophic stress states can be reversed by HDAC inhibitors and may be useful to improve cardiac structure and function in HFpEF patients.
2021-09-08 | PXD013663 | Pride