TDP-43 is an RNA/DNA-binding protein implicated in transcriptional repression and mRNA processing. Inclusions of TDP-43 are hallmarks of frontotemporal dementias and amyotrophic lateral sclerosis. Besides aggregation of TDP-43, loss of nuclear localization is observed in disease. To identify relevant targets of TDP-43, we performed an expression profiling study. Thereby, histone deacetylase 6 (HDAC6) downregulation was discovered upon TDP-43 silencing on mRNA and protein level in human embryonic kidney HEK293E and neuronal SH-SY5Y cells. This was accompanied by accumulation of the major HDAC6 substrate, acetyl-tubulin. Expression of wild-type but neither RNA-binding- nor nuclear-localization-deficient TDP-43 restored HDAC6 expression. Moreover, TDP-43 bound specifically to HDAC6 mRNA arguing for a direct functional interaction. Importantly, in vivo validation in TDP-43 knockout Drosophila melanogaster also showed HDAC6 mRNA decrease. HDAC6 is necessary for protein aggregate formation and degradation. Indeed, downregulation of HDAC6 reduced aggregate formation and increased cytotoxicity of expanded poly-glutamine ataxin-3 in TDP-43 silenced cells. This was completely restored by co-transfection with HDAC6. In conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby contribute to pathogenesis.
Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6.
Cell line
View SamplesBecause insufficiency of the Runt-related transcription factor 2 (Runx2) limits skeletal growth, there is a great deal of effort to activate Runx2 for clinical use. In this study, we found that MS-275, the class I-specific HDAC inhibitor, activates Runx2 both transcriptionally and translationally. Therefore, we performed NGS analysis to gain accurate patterns of gene expression in mouse calvaria tissue through MS-275 administration. As a result, we could get insight that treatment of MS-275 increases genes related with osteoblast differentiation and cell proliferation, and decreases genes in field of causing apoptosis. Overall design: Mice calvarial mRNA profiles of embryonic day 17.5 wild type (WT) and Runx2+/- mice were generated by deep sequencing using Illumina NextSeq 500. Mice were administered MS-275 or vehicle. Three replicates per group.
An HDAC Inhibitor, Entinostat/MS-275, Partially Prevents Delayed Cranial Suture Closure in Heterozygous Runx2 Null Mice.
Specimen part, Treatment, Subject
View SamplesHypocalcemic vitamin D analogs are appealing molecules to exploit the immunomodulatory actions of active vitamin D in vivo. The functional modulation of dendritic cells is regarded as the key mechanism underlying their ability to regulate T cell responses. In contrast, the direct actions of vitamin D and structural analogs on T lymphocytes remain less well characterized.
The vitamin D analog, TX527, promotes a human CD4+CD25highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation.
Specimen part, Subject
View SamplesTo understand epigenetic changes in the distal regulatory as well as proximal regions, we performed RNA-seq, MBD-seq, and H3K27ac ChIP-seq on gastric tissues and cell lines. Overall design: mRNA sequencing profiles of normal tissue (n), purified gastric cancer (sc), and cultured gastric cancer cell (dc) were generated by deep sequencing, in five samples from three patients (csc1, csc2, csc3) and two replicates (csc1_sc2, csc1_sc3), using Illumina GAIIx and HiSeq2000.
Integrated epigenomic analyses of enhancer as well as promoter regions in gastric cancer.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-Wide Chromatin Landscape Transitions Identify Novel Pathways in Early Commitment to Osteoblast Differentiation.
Specimen part, Cell line, Treatment, Time
View SamplesDHS enahncers identify novel pathways in OB differentiation
Genome-Wide Chromatin Landscape Transitions Identify Novel Pathways in Early Commitment to Osteoblast Differentiation.
Cell line, Treatment
View SamplesMetastatic squamous cell carcinoma suggest mTOR inhibitor as therapeutic agent because of activation of the PI3K/AKT/mTOR pathway. However, many therapeutic agents about cancer show resistance. Here, we investigated resistance network about mTOR inhibitor in skin squamous cell carcinoma using microarray. Our study identified that CCND1 overexpression increase resistance about mTOR inhibitor. The molecular mechanism may improve in therapeutic effects of mTOR inhibitor in cutaneous SCC.
Identification of mTOR inhibitor-resistant genes in cutaneous squamous cell carcinoma.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The impact of microRNAs on protein output.
No sample metadata fields
View SamplesThis array analysis is to study developmental time course of the regulation of target messages expression during culture of murine neutrophils versus miR-223 null neutrophils. Culture media was SILAC-IMDM for MS analysis.
The impact of microRNAs on protein output.
No sample metadata fields
View SamplesThis array analysis is to study the regulation of target messages expression in murine neutrophils versus miR-223 null neutrophils.
The impact of microRNAs on protein output.
No sample metadata fields
View Samples