Elevated expression of the H3K36me2 demethylase Kdm8/Jmjd5, a direct Miz1 target gene causes prolonged postnatal Schwann cell proliferation in the murine Miz1∆POZ neuropathy
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ABSTRACT:
PROVIDER: PRJEB20072 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1890750.fastq.gz | Fastqsanger.gz | |||
| ERR1890751.fastq.gz | Fastqsanger.gz | |||
| ERR1890752.fastq.gz | Fastqsanger.gz | |||
| ERR1890745.fastq.gz | Fastqsanger.gz | |||
| ERR1890746.fastq.gz | Fastqsanger.gz |
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Project description:The deletion of the POZ domain of the transcription factor Miz1 leads to a late onset neuropathy with subsequent spontaneous regeneration in mice. In this study, we aim to identify genes that are involved in the development of this neuropathy. We traced first gene regulatory changes in sciatic nerve tissue from Miz1∆POZ mice to 30 days after birth. At this time point, we harvested samples of sciatic nerve tissue from several mice and performed RNAseq analysis to identify differentially expressed genes between Miz1∆POZ and wild type mice.
2018-03-14 | E-MTAB-5600 | biostudies-arrayexpress
Project description:Mice: knock-out of the Miz1 POZ-domain in brain (Miz1DPOZNes) and control mice. The RNA expression in cerebella of of old Miz1 delta POZ mice (1.5 years), old control mice (1.5 years), young Miz1 delta POZ mice (5.5 weeks) and young control mice (5.5 weeks) was compared
2013-10-01 | E-MEXP-3878 | biostudies-arrayexpress
Project description:Previous studies have revealed that nuclear Miz1 is implicated in the regulation of several cancers mainly relying on its POZ domain. Current study, however, uncovers an unexpected function of cytoplasmic Miz1 in hepatocellular carcinoma (HCC). In vivo HCC models in Miz1 and Miz1(POZ) KO mice along with RNA-sequencing experiments show that hepatocyte specific ablation of Miz1 exacerbates TNF-α-induced NF-κB activation and promotes the progression of HCC independent of its transcriptional activity. Ubiquitination and proteosomal degradation of cytoplasmic Miz1 liberates its novel partner Metadherin (MTDH), and its site specific phosphorylation is critical to NF-κB activation. These findings reveal a brand new role of cytosolic Miz1 as a suppressor of HCC, and provide profound insights into liver cancer diagnosis and treatment.
2020-10-11 | GSE104940 | GEO
Project description:To isolate neuronal progenitor cells (NPCs), forebrains of E13.5 Miz1+/+ or Miz1-delta-POZ embryos were cut in small pieces, digested with trypsin and filtered through sterile gauze. Cells were cultivated in 2:1 DMEM/F12 supplemented with 1xB27 (Life technologies), 20 ng/ul EGF (Biomol), 20 ng/?l basic FGF (Biomol), 1 ug/ml fungizone (Gibco) and Penicillin/Streptomycin (PAA). NPCs were passaged every seven days. RNA expression of different genotypes was compared in sec. and quart. neurospheres.
2013-10-01 | E-MEXP-3883 | biostudies-arrayexpress
Project description:Medulloblastomas (MBs) are cerebellar tumors that can be classified into molecularly distinct subgroups that differ in pathology and prognosis. The mechanisms that underlie subgroup specification are largely unknown. While human SHH MBs express MYCN, Group3 (G3) MBs are associated with c-MYC (MYC) overexpression and often show metastasis that confers a poor prognosis. Although MYC proteins are thought to be functionally exchangeable, ectopic expression of Myc or N-myc in Trp53-/-;Cdkn2c-/- cerebellar granule neuron progenitors (GNPs) induces G3 and SHH MBs, respectively, demonstrating that each Myc protein has distinct biological properties. We now show that Myc and N-myc differ in their affinity to Miz1 and that Myc, but not N-myc, effectively recruits Miz1 to its target sites on chromatin. The interaction of Myc with Miz1 is required for the genesis of G3 MB. Myc suppresses ciliogenesis and âreprogramsâ the transcriptome of SHH-dependent GNPs to stem-like cells by repressing genes highly expressed in SHH MB via Miz1. Consistently, target genes of Myc/Miz1 are repressed in human G3 MBs but not in other MB subgroups. Collectively, the data show that the interaction of Myc with Miz1 is a defining hallmark of G3 MB development. In this study, we show that Myc and N-myc differ in their affinity for Miz1, and Myc/Miz1 interaction is required for Group3 medulloblastoma (MB). The gene expression profiles of these tumors were compared to our previously published Group3 MB model as well as SHH model of MB (Kawachi et al., 2012, Cancer Cell). Cerebellar granule neuron progenitors (GNPs) [dka220-222] from postnatal (P) 6 Math1-GFP;Trp53-/-;Cdkn2c-/-. For SHH medulloblastomas, [dka204-206] and [blm015-017 or dka050-dka051], spontaneous medulloblastomas from Cdkn2c-/-;Trp53Fl/Fl;Nestin-Cre (Kawachi et al., 2012, Cancer Cell) and Ptch1+/-;Cdkn2c-/- (Uziel et al., 2005, Genes Dev) were used, respectively. Myc- [dka201-203] and MycV394D (termed MycVD thereafter)- [bvo017-bvo023] tumors were from Trp53-/-;Cdkn2c-/- cerebella of P6-P7 pups. Myc/ÎPOZ tumors [bvo002-bvo006] were obtained from Trp5Fl/Fl;Miz1ÎPOZ/POZ;Nestin-Cre cerebella of P6-P7 pups.
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Project description:Lineage negative, CD44 negative, CD25 positive thymocytes were isolated from wt mice or Miz1 POZ-domain knockout mice to analyze the effect of loss of Miz1 in the DN3 population of T-cells We used the mouse Affymetrix MOE430-2 microarray to characterize global gene expression changes of DN3 thymocytes from Miz1 knockout mice. We performed microarray based gene expression profiling to determine the effect of loss of Miz1 activity on the gene expression pattern of mouse DN3 thymocytes from wt and Miz1-delta-POZ mice.
2011-08-23 | E-GEOD-28342 | biostudies-arrayexpress
Project description:RASopathies are a diverse group of developmental disorders associated with germline or somatic mutations in genes of the Mitogen Activated Protein Kinase (MAPK) signaling pathway. We characterized in this dataset a mosaic mouse model, in which a constitutively active form of the MAPK effector Braf (V600E) is expressed in the embryonic progenitors of myelin-forming Schwann cells of peripheral nerves under the control of the MpZ(P0)-Cre recombinase. These mice develop an early, fully penetrant degenerative peripheral neuropathy. The RNAseq experiment compares total RNA extracted from whole sciatic nerves between spinal cord and knee between mutant and control pairs of littermates from six distinct outbred litters at postnatal day 21.
2024-12-31 | GSE262047 | GEO
Project description:Hereditary Motor and Sensory Neuropathies (HMSN) are the most common inherited peripheral neuropathies and comprise a group of genetically heterogeneous diseases. We study the genetic defects causing three demyelinating disorders: HMSN1A, HMSN-LOM and congenital cateracts facial dysmophism neuropathy (CCFDN) syndrome, which are caused by mutations in PMP22, NDRG1 and CTDP1, respectively. The function and patho-mechanisms of these genes is still unknown. To identify effects downstream of the mutations, thereby possibly involved in the disease process, we used Serial expression of gene expression (SAGE) and microarray analysis. We analyzed human Schwann cell lines from three normal subjects, one HMSN-LOM patient, two HMSN-1A patients and two CCFDN patients and compared our data to a recent dataset of human Schwann cells (4 normal subjects passage 1 vs. 3, GDS1869/GSE4030 M.B. Bunge, 2006). We excluded genes that were not consistently regulated between biological and technical replicates and genes that were found to be influenced by passage number (p<0.05). Comparing expression profiles of demyelinating neuropathies with different mutations we identified: 1. expression signatures specific for each genotype. 2. Genes commonly (dys)regulated in all screened neuropathies. Interestingly, these include genes that play a role in reorganization of sodium channels in central and peripheral nerves (S100A10, CD90), or extracellular matrix remodeling (e.g. TGFBI, SERPINE1, THBS1). We also found high up-regulation of genes involved in Schwann cell lineage and in particular, genes that are associated with an immature or pre-myelinating Schwann cell phenotype (i.e. Sox2, Sox10, COL18A1, TFAP2A, Pax3, CDH19). Our study shows that many genes, possibly contributing to nerve pathology can be identified by this approach. Experiment Overall Design: Experimental design: in total 12 (two-color) arrays were run. All neuropathy samples were in duplicate (technical replicates). Two CCFDN and two HMSN1A patients were also analyzed as biological replicates. Three healthy subjects were included from which one was in duplicate. All samples (Cy3) were compared to a common reference pool (Cy5) which consisted of a mix of all samples.
2008-04-05 | E-GEOD-7423 | biostudies-arrayexpress
Project description:Miz1 is a zinc finger protein that regulates expression of cell cycle inhibitors as part of a complex with Myc. Cell cycle-independent functions of Miz1 are poorly understood. Here, we use a Nestin-Cre transgene to delete an essential domain of Miz1 in the central nervous system (Miz1ΔPOZNes). Miz1ΔPOZNes mice display cerebellar neurodegeneration characterized by the progressive loss of Purkinje cells. Chromatin immunoprecipitation sequencing and biochemical analyses show that Miz1 activates transcription upon binding to a non-palindromic sequence present in core promoters. Target genes of Miz1 encode regulators of autophagy and proteins involved in vesicular transport that are required for autophagy. Miz1ΔPOZ neuronal progenitors and fibroblasts show reduced autophagic flux. Consistently, polyubiquitinated proteins and p62/Sqtm1 accumulate in the cerebella of Miz1ΔPOZNes mice, characteristic features of defective autophagy. Our data suggest that Miz1 may link cell growth and ribosome biogenesis to the transcriptional regulation of vesicular transport and autophagy.
2013-09-27 | GSE48602 | GEO
Project description:DNA methylation is a key epigenetic regulator of mammalian embryogenesis and somatic cell differentiation. Using high-resolution genome-scale maps of methylation patterns, we show that the formation of myelin in the peripheral nervous system, proceeds with progressive DNA demethylation, which coincides with an upregulation of critical genes of the myelination process. More importantly, we found that, in addition to expression of DNA methyltransferases and demethylases, the levels of S-adenosylmethionine (SAMe), the principal biological methyl donor, could also play a critical role in regulating DNA methylation during myelination and in the pathogenesis of diabetic neuropathy. In summary, this study provides compelling evidence that SAMe levels need to be tightly controlled to prevent aberrant DNA methylation patterns, and together with recently published studies on the influence of SAMe on histone methylation in cancer and embryonic stem cell differentiation show that in diverse biological processes, the methylome, and consequently gene expression patterns, are critically dependent on levels of SAMe. DNA methylome maps of mouse Schwann cells in which GNMT was silenced by lentiviral vectors, cultured in normal medium or low methionine medium.
2014-01-27 | E-GEOD-51031 | biostudies-arrayexpress