Chromodomains are found in many regulators of chromatin structure. Most of them recognize methylated histones. Here, we investigate the role of the Corto chromodomain. This Drosophila melanogaster Enhancer of Polycomb and Trithorax is involved in both silencing and activation of gene expression. Overexpression of Corto chromodomain (CortoCD) in transgenic flies show that this domain is critical for Corto function and behaves as a chromatin-targeting module. Mass spectrometry analysis of peptides pulled down by CortoCD from nuclear extracts reveals that they correspond to nuclear ribosomal proteins (RPs). Notably, CortoCD binds with high affinity RPL12 tri-methylated on lysine 3 (RPL12K3me3) as demonstrated by real-time interaction analyses. Co-localization of Corto and RPL12 with active epigenetic marks on polytene chromosomes suggests that they are involved in fine-tuning transcription of genes located in open chromatin. Hence, pseudo-ribosomal complexes composed of various RPs might participate in regulation of gene expression in connection with chromatin regulators. RNA-seq analysis of wing imaginal discs overexpressing either Corto or RPL12 show that most deregulated genes are shared by both factors. Interestingly, these common targets are enriched in RP genes suggesting that Corto and RPL12 are involved in dynamic coordination of ribosome biogenesis. Overall design: To address the role of Corto and RPL12 in regulation of transcription, we deep-sequenced transcripts of wing imaginal discs from third instar larvae over-expressing either FH-cortoCD or RpL12-Myc under control of the wing-specific scalloped::Gal4 driver (sd::Gal4>UAS::FH-cortoCD or sd::Gal4>UAS::RpL12-Myc). Total RNA from FH-cortoCD or RpL12-Myc, the sd::Gal4/+ control or a w1118 reference line were isolated from pools of wing imaginal discs and subjected to RNA-seq on an Illumina high throughput sequencer.
New partners in regulation of gene expression: the enhancer of Trithorax and Polycomb Corto interacts with methylated ribosomal protein l12 via its chromodomain.
Specimen part, Subject
View SamplesHere we analyse single cell transcriptome profiles of EZH2-deficient human embroynic stem cells Overall design: Single cell transcriptome (mRNA-Seq) from Ezh2-/- (Null) and EZH2+/+ (WT) human ESC
Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells.
Specimen part, Subject
View SamplesThe homeobox containing gene Arx is expressed during ventral telencephalon development and it is required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose syntoms are compatible with a loss of cortical interneurons and altered basal ganglia related-activities in humans. Herein, we reported the identification by global expression profiling of a group of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Following analysis revealed the striking ectopic expression in the ganglionic eminences of a number of genes normally not, or only marginally, expressed in the ventral telencephalon. Among them, we functionally analyzed Ebf3, whose ectopic expression in ventral telencephalon is preventingneuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissue might marginally rescue tangential cell movements. Together, these data provide an initial analysis of the molecular pathways regulated by Arx and how their networking might regulate those specific cellular processes during telencephalon development strongly altered by loss of Arx.
Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.
Specimen part
View SamplesInnate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been studied extensively in model organisms, little is known about these first responders in humans, especially their lineage and functional kinships to cytokine-secreting T helper cell (Th) counterparts. Here, we report gene regulatory circuitries for four human ILCTh counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells, but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell identity genes in each lineage, uncovering new modes of regulation for signature cytokines, novel molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILCTh subsets.
Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.
Specimen part
View SamplesPressure overload-induced cardiac hypertrophy was examined in IL-18 knockout and littermate control mice.
Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload.
Specimen part
View SamplesThe 6-hydroxydopamine (6OHDA) rat model of parkinsonism is among the first, and most commonly used, animal models of Parkinsons disease. It provides insight into the compensatory changes that occur in the brain after dopamine (DA) neuron degeneration. In order to better define the consequences of substantia nigra DA neuron loss on the neural and glial populations during and following nigrostriatal degeneration, tissue was collected and evaluated from the substantia nigra of 6OHDA or vehicle treated, or nave rats at 1, 2, 4, 6 & 16 weeks.
The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.
Sex, Specimen part
View SamplesThe subsets of immune cells within the human placenta are incompletely described. We used microarray to determine the transcriptional differences between two myeloid subsets in the term human placenta.
Two Distinct Myeloid Subsets at the Term Human Fetal-Maternal Interface.
Specimen part
View SamplesRationale: Pulmonary arterial hypertension is a common and potentially fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. The ability to identify patients at risk for developing pulmonary hypertension would be clinically beneficial.
Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension.
Sex, Specimen part, Disease, Disease stage
View SamplesThe molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. In addition, the gene expression changes associated with activation of primary human hepatic stellate cells, a key event during fibrogenesis, remain poorly characterized. Here, we provide the transriptomic profile underpinning the healthy phenotype of human hepatocytes, liver sinusoidal endothelial cells (LSECs) and quiescent hepatic stellate cells (qHSCs) as well as activated HSCs (aHSCs)
Genome-wide analysis of DNA methylation and gene expression patterns in purified, uncultured human liver cells and activated hepatic stellate cells.
Sex, Age, Specimen part, Subject
View Samples