Comparison of rosette leaves of two different RAP2.2 overexpressing lines with wild type leaves. The AP2/EREBP transcription factor RAP2.2 was shown to bind to a cis-acting motif within the phytoene synthase promoter from Arabidopsis. To investigate effects of increased RAP2.2 levels, two RAP2.2 overexpressing Arabidopsis thaliana (ecotype Wassilewskija) lines were generated: one line, nosr2, carried the nos promoter and showed a two-fold increase in RAP2.2 transcript level, the second line, cmr-5, carried four copies of the CaMV-35S enhancer and showed a 12-fold increase. However, neither weak nor strong increase in RAP2.2 transcript amounts had any effect on RAP2.2 protein levels as shown by Western blot analysis. The strong robustness of RAP2.2 protein levels towards transcriptional changes can be explained by specific protein degradation which includes SINAT2, an E3 ubiquitin ligase which was isolated using a two-hybrid approach. Accordingly, global gene expression analysis using both RAP2.2 overexpressing lines showed only minor transcriptional changes which are probably due to minor growth variation than to mechanisms involved in the down-regulation of RAP2.2 protein amounts.
Transcription factor RAP2.2 and its interacting partner SINAT2: stable elements in the carotenogenesis of Arabidopsis leaves.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Specimen part
View SamplesDOT1L as methyltransferase of H3K79 is implicated in brian development. Here, we further defined DOT1L function in gene expression during cerebellar development using Microarrays. For that we generated Dot1l knockout mice using a Atoh-Cre driver line resulting in a Dot1l knockout within the cerebellum. The RNA of cerebellar tissue of the Dot1l knockout animals was thereby compared to controls. Additionally we compared the RNA levels of cultured CGNP and CGN samples treated with a DOT1L inhibitor versus DMSO treated cells. The data sets reveals potential new gene expression targets of DOT1L in vivo and in vitro, which ensure a correct development of the cerebellum.
Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Specimen part
View SamplesWOX5 maintains columella stem cells in the Arabidopsis root and prevents their differentiation. In order to understand the molecular mode of WOX5 action the genes differentially expressed by WOX5 inducible over-expression were determined by analysis of microarray hybridizations. Seedlings transformed with a dexamethasone inducible WOX5 construct were induced for one or four hours with dexamethasone or a mock solution. Other seedlings were treated one hour with cycloheximide ( a protein synthesis inhibitor to reduce secondary transcriptional effects after WOX5 activation) and either dexamethasone or a mock solution. Root tips were harvested, RNA extracted, and the RNA samples prepared for hybridization to Affymetrix microarrays. Potential target genes of WOX5 were further analyzed by transcriptional markers, qPCR and EMSA (electrophoretic mobility shift assay).
Organizer-Derived WOX5 Signal Maintains Root Columella Stem Cells through Chromatin-Mediated Repression of CDF4 Expression.
Specimen part, Compound, Time
View SamplesGene expression of human liver cells at different developmental stages.
No associated publication
Sex, Age, Specimen part
View SamplesOpen chromatin is induced locally during the repair of DNA double strand breaks, when a cascade of protein recruitments and modifications is triggered. This "ATM cascade" includes components like the Mrn complex, ATM kinase, phosphorylated histon variant ?H2AX, MDC1, E3 ligases RNF 8 and RNF8, 53BP1, and Rif1. Recent investigations have shown that also the Mad2l2 protein is a downstream effector of the ATM cascade during DNA repair. It was first described as an accessory subunit during translesion DNA repair, and more recently as a key factor inhibiting the resection of DNA 5`ends, thus promoting non-homologous end joining, and repressing homologous recombination.Naive embryonic stem cells (ESCs) have a globally open chromatin. A preliminary study from this laboratory has demonstrated that ESCs require the presence of the Mad2l2 protein for the maintenance of their transcriptional and epigenetic profiles, and thus for the stability of pluripotency (Pirouz et al., Cell Cycle 14, 1596, 2015). The aim of the present study was to correlate Mad2l2 with the ATM cascade and the chromatin status in ESCs.
No associated publication
Sex, Specimen part, Cell line
View SamplesTemozolomide (TMZ) is a frequently used chemotherapy for glioma; however, chemoresistance is a major problem limiting its effectiveness. Thus knowledge of mechanisms underlying this outcome could improve patient prognosis. Here, we report that deletion of a regulatory element in the HOTAIR locus increases glioma cell sensitivity to TMZ and alters transcription of multiple genes. Analysis of a combination of RNA-seq, Capture HiC and patient survival data suggests that CALCOCO1 and ZC3H10 are target genes repressed by the HOTAIR regulatory element and that both function in regulating glioma cell sensitivity to TMZ. Rescue experiments and TAD analysis based on HiC data confirmed this hypothesis. We propose a new regulatory mechanism governing glioma cell TMZ sensitivity.
No associated publication
No sample metadata fields
View SamplesTo analyze the role of DNA methylation during differentiation, we performed genome-wide expression analysis of undifferentiated wild type, dnmt1-/- and triple knock out (TKO; dnmt1-/-, dnmt3a-/-, dnmt3b-/-) ESCs as well as respective embryoid bodies (EBs) at two stages of differentiation
Global DNA hypomethylation prevents consolidation of differentiation programs and allows reversion to the embryonic stem cell state.
Specimen part
View SamplesRNA-SEQ of Arabidopsis thaliana leaf tissues under normal and low CO2
No associated publication
Specimen part
View SamplesAlterations in the tissue microenvironment collaborate with cell autonomous genetic changes to contribute to neoplastic progression. The importance of the microenvironment in neoplastic progression is underscored by studies demonstrating that fibroblasts isolated from a tumor stimulate the growth of preneoplastic and neoplastic cells in xenograft models. Similarly, senescent fibroblasts promote preneoplastic cell growth in vitro and in vivo. Because senescent cells accumulate with age, their presence is hypothesized to facilitate preneoplastic cell growth and tumor formation in older individuals. To identify senescent stromal factors directly responsible for stimulating preneoplastic cell growth, we carried out whole genome transcriptional profiling and compared senescent fibroblasts to their younger counterparts. We identified osteopontin (OPN) as one of the most highly elevated transcripts in senescent fibroblasts. Importantly, reduction of OPN protein levels by RNAi did not impact senescence induction in fibroblasts; however, it dramatically reduced the growth-promoting activities of senescent fibroblasts in vitro and in vivo, demonstrating that OPN is necessary for paracrine stimulation of preneoplastic cell growth. In addition, we found that recombinant OPN was sufficient to stimulate preneoplastic cell growth. Finally, we demonstrate that OPN is expressed in senescent stroma within preneoplastic lesions that arise following DMBA/TPA treatment of mice, suggesting that stromal-derived OPN-mediated signaling events impact neoplastic progression.
Senescent stromal-derived osteopontin promotes preneoplastic cell growth.
No sample metadata fields
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