Precise 5' splice site recognition is essential for both constitutive and regulated pre-mRNA splicing. The U1 snRNP specific protein U1C is involved in this first step of spliceosome assembly and important for stabilizing early splicing complexes. We used an embryonically lethal U1C knockout mutant zebrafish, hi1371, to investigate the potential genomewide role of U1C for splicing regulation. Surprisingly, genomewide RNA-Seq analysis of mutant versus wildtype embryos revealed a large set of specific target genes that changed their alternative splicing patterns in the absence of U1C. In sum, our findings provide evidence for a new role of a general snRNP protein, U1C, as a mediator of alternative splicing regulation.
RNA-Seq analysis in mutant zebrafish reveals role of U1C protein in alternative splicing regulation.
None
No sample metadata fields
View SamplesWe analysed the G-actin regulated transcriptome by gene expression analysis using previously characterised actin binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF) as well as unknown directly regulated genes.
Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.
Time
View SamplesZygotic genome activation (ZGA), which is according to the midblastula transition in zebrafish, is an important event during the maternal-zygotic transition in animals. Our preliminary study and other groups works indicate that epigenetic regulations play an essential role in ZGA.
Protein Arginine Methyltransferase 6 (Prmt6) Is Essential for Early Zebrafish Development through the Direct Suppression of gadd45αa Stress Sensor Gene.
Age, Specimen part
View SamplesWe performed RNA-sequencing on four groups of zebrafish larvae: control, Tg(Myc), Tg(Kras), Tg(Myc)&Tg(Kras) to analyze the expression of genes involved in the lipid-associated pathways.The results revealed high dynamic alterations in almost all aspects of lipid metabolism, among which, the expressions of genes involved in TG/DG/GP transformation and FA desaturation/elongation displayed intensive changes, in consistent with our observations in lipodomics profiling
No associated publication
None
No sample metadata fields
View SamplesThe WHV/c-myc transgenic mouse is an animal model of hepatocarcinogenesis that can exquisitely mimic the cancer staging in human Hepatocellular carcinoma (HCC), in which the c-myc oncogene is activated by adjacent woodchuck hepatitis virus (WHV) DNA sequences. Compared to other models of c-myc transgenic mice, WHV/c-myc mice stably develop HCC with a relatively short latent period of 8 to 12 months, with a high (near 100%) tumor incidence.
No associated publication
Age
View SamplesOBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX and NUP98-HOX fusion proteins to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. MATERIALS AND METHODS: To further resolve these mechanisms, we conducted a structure-function analysis of MEIS1 and gene-expression profiling, in the context of NUP98-HOXD13 (ND13) leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the PBX-interaction domain, the homeodomain, and the C-terminal domain of MEIS1, are all required for leukemogenic collaboration with ND13. In contrast, the N-terminal domain of MEIS1 is dispensable for collaboration with ND13, but is required for Flt3 upregulation, indicating additional roles for MEIS1 in induction of leukemia independent of alterations in Flt3 expression. Gene-expression profiling of a cloned ND13 preleukemic cell line transduced with wild-type or Meis1 mutant forms revealed deregulation of multiple genes, including a set not previously implicated as MEIS1 targets. Chromatin immunoprecipitation revealed the in vivo occupancy of MEIS1 on regulatory sequences of Trib2, Flt3, Dlk1, Ccl3, Ccl4, Pf4, and Rgs1. Furthermore, engineered overexpression of Trib2 complements ND13 to induce AML while Ccl3 potentiates the repopulating ability of ND13. CONCLUSION: This study shows that Meis1-induced leukemogenesis with ND13 can occur in the absence of Flt3 upregulation and reveals the existence of other pathways activated by MEIS1 to promote leukemia.
Linkage of Meis1 leukemogenic activity to multiple downstream effectors including Trib2 and Ccl3.
Specimen part
View SamplesHearts of Myh6-MeCP2 transgenic mice and wildtype littermates were rapidly dissected and flash frozen.
Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure.
Specimen part
View SamplesTranscriptom analysis of stellate sympathetic ganglia after 8 weeks of cardiac pressure overload caused by transverse aortic constriction.
Sympathetic alpha(2)-adrenoceptors prevent cardiac hypertrophy and fibrosis in mice at baseline but not after chronic pressure overload.
Sex
View SamplesDrd2 regulates striatal gene networks.
Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin.
Specimen part
View SamplesL-3,4-dihydroxyphenylalanine (levodopa) treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). While it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type-specific gene expression changes that occur in sub-classes of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes whose expression is correlated with levodopa dose, many of which are under the control of AP-1 and ERK signaling. In spite of homeostatic adaptations involving several signaling modulators, AP-1-dependent gene expression remains highly dysregulated in direct pathway SPNs (dSPNs) upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease.
Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia.
Specimen part, Treatment
View Samples