Whole transcriptome for SKI knock-out and control HL60 cells was sequenced. SKI control and knockout samples were compared to find differentially expressed genes. Differentially expressed genes were further analysed to find the significance of SKI in HL60 cells. Overall design: Examining of SKI dependent transcriptome in HL60 cells using RNAseq.
Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1.
Specimen part, Cell line, Subject
View SamplesThe p53 family is known as a family of transcription factors with functions in tumor suppression and development. Whereas the central DNA binding domain is highly conserved among the three family members p53, p63 and p73, the C-terminal domains (CTDs) are diverse and subject to alternative splicing and post-translational modification. Here we demonstrate that the CTDs strongly influence DNA binding and transcriptional activity. While p53 and the p73 isoform p73gamma have basic CTDs and form weak sequence-specific protein-DNA complexes, the major p73 isoforms alpha, beta and delta have neutral CTDs and bind DNA strongly. A basic CTD has been previously shown to enable sliding along the DNA backbone and to facilitate the search for binding sites in the complex genome. Our experiments, however, reveal that a basic CTD also reduces protein-DNA complex stability, intranuclear mobility, promoter occupancy in vivo, transgene activation and induction of cell cycle arrest or apoptosis. A basic CTD in p53 and p73gamma therefore provides both positive and negative regulatory functions presumably to enable rapid switching of protein activity in response to stress. In contrast, most p73 isoforms exhibit constitutive DNA binding activity consistent with a predominant role in developmental control.
C-terminal diversity within the p53 family accounts for differences in DNA binding and transcriptional activity.
No sample metadata fields
View SamplesInterference with chemoresistance to enhance the efficacy of chemotherapeutics may be of great utility for cancer therapy. We have identified KINK-1 (Kinase Inhibitor of NF-kappaB-1), a highly selective small-molecule IKKkappa inhibitor, as a potent suppressor of both constitutive and induced NF-kappaB activity in melanoma cells. While KINK-1 profoundly diminished various NF-kappaB-dependent gene products regulating proliferation, cytokine production or anti-apoptotic responses, the compound by itself showed little antiproliferative or pro-apoptotic activity on the cellular level. However, its combination with some cytostatics markedly enhanced their antitumoral activities in vitro, and doxorubicin-induced NF-kappaB activation, a mechanism implicated in chemoresistance, was abrogated by KINK-1. In addition, when KINK-1 was combined with doxorubicin in an in vivo melanoma model, experimental metastasis was significantly diminished as compared to either treatment alone. Induction of chemoresistance by KINK-1 in vivo was not observed. Thus, KINK-1 or related substances might increase the susceptibility of tumors to chemotherapy.
KINK-1, a novel small-molecule inhibitor of IKKbeta, and the susceptibility of melanoma cells to antitumoral treatment.
No sample metadata fields
View Samplessh RNA of p73 in Fibroblasts compared to non-silencing control
p73 poses a barrier to malignant transformation by limiting anchorage-independent growth.
No sample metadata fields
View SamplesWhole transcriptome for PRMT6 knock-out and control NT2/D1 cells with and without ATRA (all-trans retinoic acid) was sequenced. These samples were compared to each other to find differentially regulated genes and PRMT6-dependent transcriptome in pluripotency and differentiating cells. Overall design: Examining of PRMT6-dependent transcriptome in NT2/D1 cells using RNAseq.
Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the Transcriptional Outcome of Associated Genes.
Specimen part, Cell line, Subject
View SamplesDiagnostic samples of peripheral blood form acute myeloid leukemia were analysed for gene expression differences
NFATc1 as a therapeutic target in FLT3-ITD-positive AML.
Sex, Specimen part
View SamplesThe recruitment of mesenchymal stem cells in order to reconstruct damaged cartilage of osteoarthritis joints is a challenging tissue engineering task. Vision towards this goal is blurred by a lack of knowledge about the underlying differences between chondrocytes and MSC during the chondrogenic cultivation process. The aim of this study was to shed light on the differences between chondrocytes and MSC occurring during chondral differentiation through tissue engineering.
Expression pattern differences between osteoarthritic chondrocytes and mesenchymal stem cells during chondrogenic differentiation.
Specimen part
View SamplesAbiotic stress is a major factor for crop productivity, a problem likely to be exacerbated by climate change. Improving the tolerance to environmental stress is one of the most important goals of crop breeding programmes. While the early responses to abiotic stress in plants are well studied, plant adaptation to enduring or recurring stress conditions has received little attention. This project investigates the molecular mechanism of the maintenance of acquired thermotolerance as a model case of stress memory in Arabidopsis. Arabidopsis seedlings acquire thermotolerance through a heat treatment at sublethal temperatures. To investigate the underlying mechanisms, we are investigating changes in the transcriptome at two timepoints after a heat acclimation treatment using Arabidopsis thaliana seedlings.
Arabidopsis miR156 Regulates Tolerance to Recurring Environmental Stress through SPL Transcription Factors.
Treatment
View SamplesThe histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cells (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL (Male-Specific Lethal) and NSL (Non-specific lethal). The individual contribution of MSL and NSL complexes to transcription regulation in mESCs is not well understood. Our genome-wide analysis of MSL and NSL localization show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds at promoters, iii) while MSL binds in gene bodies. Knockdown of Msl1 leads to a global loss of histone H4K16ac indicating that MSL is the main HAT acetylating H4K16 in mESCs. MSL was enriched at many mESC-specific genes, but also at bivalent domains. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs. Furthermore, MSL is essential for the regulation of key mESC-specific and bivalent developmental genes.
Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation.
No sample metadata fields
View SamplesRecent studies have identified intracellular metabolism as a fundamental determinant of macrophage function. In obesity, proinflammatory macrophages accumulate in adipose tissue and trigger chronic low-grade inflammation, that promotes the development of systemic insulin resistance, yet changes in their intracellular energy metabolism are currently unknown. We therefore set out to study metabolic signatures of adipose tissue macrophages (ATMs) in lean and obese conditions. F4/80-positive ATMs were isolated from obese vs lean mice. High-fat feeding of wild-type mice and myeloid-specific Hif1-/- mice was used to examine the role of hypoxia-inducible factor-1 (HIF-1) in ATMs part of obese adipose tissue. In vitro, bone marrow-derived macrophages were co-cultured with adipose tissue explants to examine adipose tissue-induced changes in macrophage phenotypes. Transcriptome analysis, real-time flux measurements, ELISA and several other approaches were used to determine the metabolic signatures and inflammatory status of macrophages. In addition, various metabolic routes were inhibited to determine their relevance for cytokine production. Transcriptome analysis and extracellular flux measurements of mouse ATMs revealed unique metabolic rewiring in obesity characterised by both increased glycolysis and oxidative phosphorylation. Similar metabolic activation of CD14+ cells in obese individuals was associated with diabetes outcome. These changes were not observed in peritoneal macrophages from obese vs lean mice and did not resemble metabolic rewiring in M1-primed macrophages. Instead, metabolic activation of macrophages was dose-dependently induced by a set of adipose tissue-derived factors that could not be reduced to leptin or lactate. Using metabolic inhibitors, we identified various metabolic routes, including fatty acid oxidation, glycolysis and glutaminolysis, that contributed to cytokine release by ATMs in lean adipose tissue. Glycolysis appeared to be the main contributor to the proinflammatory trait of macrophages in obese adipose tissue. HIF-1, a key regulator of glycolysis, nonetheless appeared to play no critical role in proinflammatory activation of ATMs during early stages of obesity. Our results reveal unique metabolic activation of ATMs in obesity that promotes inflammatory cytokine release. Further understanding of metabolic programming in ATMs will most likely lead to novel therapeutic targets to curtail inflammatory responses in obesity.
Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses.
Sex, Specimen part
View Samples