Ptf1a was identified as the essential transcription factor which controls pancreatic exocrine enzyme expression. With lineage tracing eperiments Ptf1a was recognized as an important pancreatic progenitor transcription factor and Ptf1a null mice do not develop a pancreas.
RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors.
Specimen part
View SamplesTumor-infiltrating macrophages, NK cells, CD8+ and CD4+ T cells sorted from clear cell renal cell carcinoma patient specimens. Overall design: 4 macrophage samples (CD45+CD3-CD56-CD14+), 2 CD16+ NK cell samples (CD45+CD3-CD56+CD16+), 5 CD8+ T cell samples (CD45+CD3+CD8+), 3 CD4+ T cell samples (CD45+CD3+CD4+), and one non-immune cell sample (CD45-).
Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures.
Specimen part, Disease, Subject
View SamplesTo assay the effect of depletion of the RNA exosome on RNAs shorter than the standard length captured by RNA-seq (>200 nt), we created RNA-seq libraries using fragmented RNA and a linker-ligation-based protocol that does not deplete RNAs shorter than 200 nt. Note: these data relate to Figure 6E in Lubas, Andersen et al., Cell Reports 2014 (accepted) Overall design: These samples constitute RNA-seq libraries prepared to enrich for short RNA fragments such as snRNA and snoRNAs. Three different HeLa cell RNAi experiments were used to generate the RNA samples applied in the library construction: control transfected, hRRP40-depleted and triple-depleted of the known RNA exosome-associated ribonucleases (DIS3, DIS3L and hRRP6 knock-down). By these means the data offers reveal RNA exosome substrates via their up-regulation in the respective knock-downs NOTE: The ''Figure6E_RNAseq_DataTable_PlottedValues.txt'' was generated from total 5 samples, with two additional published samples [SRP031620] and provided to better allow readers to fully replicate the analyses presented in the publication.
The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis.
No sample metadata fields
View SamplesmRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. Overall design: mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.
Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer.
No sample metadata fields
View Samplesto explore possible treatment targets and reasons for agressive children cacners by comprehensive molecular profiling on several platforms
Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer.
No sample metadata fields
View SamplesRat kidney in normo- and hypotensive animals.
A physiogenomic approach to study the regulation of blood pressure.
No sample metadata fields
View SamplesMaintenance and maturation of primordial germ cells is controlled by complex genetic and epigenetic cascades, and disturbances in this network lead to either infertility or malignant aberration. Transcription factor Tcfap2c / TFAP2C has been described to be essential for primordial germ cell maintenance and to be upregulated in several human germ cell cancers. Using global gene expression profiling, we identified genes deregulated upon loss of Tcfap2c in primordial germ cell-like cells. We show that loss of Tcfap2c affects many aspects of the genetic network regulating germ cell biology, such as downregulation maturation markers and induction of markers indicative of somatic differentiation, cell cycle, epigenetic remodeling, and pluripotency associated genes. Chromatin-immunoprecipitation analyses demonstrated binding of Tcfap2c to regulatory regions of deregulated genes (Sfrp1, Dmrt1, Nanos3, c-Kit, Cdk6, Cdkn1a, Fgf4, Klf4, Dnmt3b and Dnmt3l) suggesting that these genes are direct transcriptional targets of Tcfap2c in primordial germ cells. Since Tcfap2c deficient primordial germ cell like cells display cancer related deregulations in epigenetic remodeling, cell cycle and pluripotency control, the Tcfap2c-knockout allele was bred onto 129S2/Sv genetic background. There, mice heterozygous for Tcfap2c develop germ cell cancer with high incidence. Precursor lesions can be observed as early as E16.5 in developing testes displaying persisting expression of pluripotency markers. We further demonstrate, that mice with a heterozygous deletion of the Tcfap2c target gene Nanos3 are also prone to develop teratoma. These data highlight Tcfap2c as a critical and dose-sensitive regulator of germ cell fate.
Transcription factor TFAP2C regulates major programs required for murine fetal germ cell maintenance and haploinsufficiency predisposes to teratomas in male mice.
Specimen part
View SamplesThe RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFalpha mRNA decay via a 3''UTR constitutive decay element (CDE). Here, we applied PAR-CLIP to human RC3H1 to identify about 3800 mRNA targets with more than 16000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage induced mRNAs, indicating a role of this RNA-binding protein in the posttranscriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of NF-kB pathway regulators such as IkBalpha and A20. RC3H1 uses roquin and Zn-finger domains to contact a binding site in the A20 3''UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with IkB kinase and NF-kB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-kB pathway. Overall design: We measured global mRNA decay rates in mock and RC3H1/RC3H2-depleted HEK293 cells. Transcription was blocked by Actinomycin D zero, one or two hours before harvesting. Total RNA was isolated in two biological replicates and subjected to polyA selection followed by high-throughput sequencing.
RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κB pathway.
No sample metadata fields
View SamplesNitrogen (N) and nitrate (NO3-) per se regulate many aspects of plant metabolism, growth and development. N/NO3- also suppresses parts of secondary metabolism including anthocyanin synthesis. Molecular components for this repression are unknown. We report that three N/NO3--induced members of the LATERAL ORGAN BOUNDARY DOMAIN (LBD) gene family of transcription factors (LBD37, LBD38 and LBD39) act as negative regulators of anthocyanin biosynthesis in Arabidopsis (Arabidopsis thaliana). Over-expression of each of the three genes in the absence of N/NO3- strongly suppresses the key regulators of anthocyanin synthesis PAP1 and PAP2, genes in the anthocyanin-specific part of flavonoid synthesis, as well as cyanidin- but not quercetin- or kaempferol-glycoside production. Conversely, lbd37, lbd38 or lbd39 T-DNA insertion mutants accumulate anthocyanins when grown in N/NO3--sufficient conditions and show constitutive expression of anthocyanin biosynthetic genes. The LBD genes also repress many other known N-responsive genes including key genes required for NO3- uptake and assimilation, resulting in altered NO3- content, nitrate reductase activity/activation, protein, amino acid and starch levels, and N-related growth phenotypes. The results identify LBD37 and its two close homologs as novel repressers of anthocyanin biosynthesis and N-availability signals in general. They also show that besides being developmental regulators LBD genes fulfill roles in metabolic regulation.
Members of the LBD family of transcription factors repress anthocyanin synthesis and affect additional nitrogen responses in Arabidopsis.
Age, Specimen part, Treatment
View Samples