Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression.
dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing.
Cell line
View SamplesMicroRNAs (miRNAs) play important roles in modulating gene expression at the post-transcriptional level. In postnatal oligodendrocytes, the miRNA expression profile -microRNAome - consists of 98 miRNAs whose expression dynamically changes during the transition from A2B5+ oligodendrocyte progenitor cells to premyelinating GalC+ cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is down-regulated during oligodendrocyte differentiation. In addition, miR-9 expression levels inversely correlate with the expression of its predicted targets, among which is the peripheral myelin protein, PMP22. PMP22 mRNA but not protein is detectable in oligodendrocytes, while Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3 untranslated region of PMP22 and down-regulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome.
Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes.
No sample metadata fields
View SamplesHypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques.
A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients.
Cell line
View SamplesThe essential thiol antioxidant, glutathione (GSH) is recruited into the nucleus of mammalian cells early in cell proliferation, suggesting a key role of the nuclear thiol pool in cell cycle regulation. However, the functions of nuclear GSH (GSHn) and its integration with the cytoplasmic GSH (GSHc) pools in whole cell redox homeostasis and signaling are unknown. Here we show that GSH is recruited into the nucleus early in cell proliferation in Arabidopsis thaliana, confirming the requirement for localization of GSH in the nucleus as a universal feature of cell cycle regulation.
Recruitment of glutathione into the nucleus during cell proliferation adjusts whole-cell redox homeostasis in Arabidopsis thaliana and lowers the oxidative defence shield.
Treatment
View SamplesThe hst3hst4 strain (FY background) has the HST3 and HST4 genes, encoding putative NAD-dependent deacetylases that regulate histone 3 K56 acetylation, deleted. Expression profiling using Affymetrix microarrays was used to assess the change in the gene expression in this strain in comparison to wild-type under normal growth conditions.
Histone H3 K56 hyperacetylation perturbs replisomes and causes DNA damage.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The transcription factor ABI4 Is required for the ascorbic acid-dependent regulation of growth and regulation of jasmonate-dependent defense signaling pathways in Arabidopsis.
Age, Specimen part
View SamplesThe role of abscisic acid (ABA) signalling in the ascorbic acid (AA)-dependent control of plant growth and defence was determined using the vtc1 and vtc2 mutants, which have impaired ascorbic acid synthesis, and in the abi4 mutant that is impaired in ABA-signalling. ABA levels were increase in the mutants relative to the wild type (Col0). Like vtc1 the vtc2 mutants have a slow growth relative to Col0. However, the wild type phenotype is restored in the abi4vtc2 double mutant. Similarly, the sugar sensing phenotype of in the abi4 is reversed in the abi4vtc2 double mutant. The vtc1 and vtc2 leaf transcriptomes show up to 70 % homology with abi4. Of the transcripts that are altered in the mutants a relative to Col0, only a small number are reversed in the abi4vtc2 double mutants relative to either abi4 or vtc2. We conclude that AA controls growth via an ABA and abi4-dependent signalling pathway. The vtc and abi4 mutants have enhanced glutathione levels and common redox signalling pathways leading to similar gene expression patterns.
The transcription factor ABI4 Is required for the ascorbic acid-dependent regulation of growth and regulation of jasmonate-dependent defense signaling pathways in Arabidopsis.
Age, Specimen part
View SamplesThe role of abscisic acid (ABA) signalling in the ascorbic acid (AA)-dependent control of plant growth and defence was determined using the vtc1 and vtc2 mutants, which have impaired ascorbic acid synthesis, and in the abi4 mutant that is impaired in ABA-signalling. ABA levels were increase in the mutants relative to the wild type (Col0). Like vtc1 the vtc2 mutants have a slow growth relative to Col0. However, the wild type phenotype is restored in the abi4vtc2 double mutant. Similarly, the sugar sensing phenotype of in the abi4 is reversed in the abi4vtc2 double mutant. The vtc1 and vtc2 leaf transcriptomes show up to 70 % homology with abi4. Of the transcripts that are altered in the mutants a relative to Col0, only a small number are reversed in the abi4vtc2 double mutants relative to either abi4 or vtc2. We conclude that AA controls growth via an ABA and abi4-dependent signalling pathway. The vtc and abi4 mutants have enhanced glutathione levels and common redox signalling pathways leading to similar gene expression patterns.
The transcription factor ABI4 Is required for the ascorbic acid-dependent regulation of growth and regulation of jasmonate-dependent defense signaling pathways in Arabidopsis.
Age, Specimen part
View SamplesTo uncover new molecular mechanisms involved in IgAN pathogenesis, we compared the genomic profiles of 12 IgAN patients with 8 healthy subjects,
Altered modulation of WNT-beta-catenin and PI3K/Akt pathways in IgA nephropathy.
Sex
View SamplesMycophenolic acid (MPA), an immunosuppressive drug widely used in kidney transplantation, has been suggested to have anti-fibrotic effects.
The anti-fibrotic effect of mycophenolic acid-induced neutral endopeptidase.
No sample metadata fields
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