We used microarrays to detail the global programme of gene expression underlying the disease progression in the mutant mice compared to their control littermates.
Microarray expression analysis and identification of serum biomarkers for Niemann-Pick disease, type C1.
Sex, Specimen part, Treatment
View SamplesHuman brain structure and size requires regulated division of neural stem cells (NSCs). NSCs undergo precise divisions to self-renew and to produce intermediate neural progenitors (INPs) and neurons. The factors that regulate NSC divisions remain poorly understood, as do mechanistic explanations of how aberrant NSC division causes reduced brain size, as seen in microcephaly. Here we demonstrate that Magoh, a component of the core exon junction complex (EJC) that binds spliced RNA, controls cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly due to INP depletion, neuronal apoptosis, and improper mitotic spindle orientation. Defective mitosis underlies these phenotypes as depletion of EJC components disrupts mitotic spindle integrity, chromosome number and genomic stability. We show that an essential function of Magoh is to regulate expression of the human microcephaly protein, LIS1, and that Lis1 addition rescues neurogenesis defects caused by Magoh knockdown, thus providing a genetic explanation for the microcephaly. This study uncovers new requirements for the EJC in brain development, NSC maintenance, mitosis and chromosome stability, thus implicating this complex in the pathogenesis of microcephaly.
The exon junction complex component Magoh controls brain size by regulating neural stem cell division.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes.
Specimen part, Cell line
View SamplesWe performed ChIP-Seq analysis of SOX10, histone H3 lysine 27 acetylation (H3K27ac) and H3K27 trimethylation (H3K27me3) in melanocytes to profile the genomic binding sites of SOX10 and the chromatin landscape. In parallel, we generated Sox10 haploinsufficient cell lines using gene knockout approaches and conducted microarray gene expression analysis to identify functional gene targets of SOX10 transcriptional regulation in melanocytes. We demonstrate that SOX10 predominantly engages open chromatin, binds to melanocyte enhancer elements and plays a central role in transcriptional activation and repression of functionally distinct classes of genes. Furthermore, we identified cis-regulatory sequence motifs of putative co-regulatory transcription factors that define SOX10-activated and SOX10-repressed target genes. Our results uncover novel mechanisms and roles of SOX10 in global transcriptional regulation of diverse regulatory pathways in the melanocyte lineage.
Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes.
Specimen part
View SamplesObesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein metabolism is not well studied. Here, we performed comparative polysome and associated transcriptional profiling analyses to study the dynamics and functional implications of endoplasmic reticulum (ER)-associated protein synthesis in the mouse liver under conditions of obesity and nutrient deprivation.
Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting.
Sex, Age, Specimen part
View SamplesWe describe and illustrate the use of a method to measure nascent nuclear gene transcription with an Array-based Nuclear Run-On (ANRO) assay using commercial microarray platforms.
Time-dependent c-Myc transactomes mapped by Array-based nuclear run-on reveal transcriptional modules in human B cells.
Cell line, Treatment
View SamplesThe regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. RI transfected cells exhibit hyper-proliferative growth and RII transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RI, RII, and parental OVCAR cells.
Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells.
No sample metadata fields
View SamplesIn Caenorhabditis elegans, VA and VB motor neurons arise as lineal sisters but synapse with different interneurons to regulate locomotion. VA-specific inputs are defined by the UNC-4 homeoprotein and its transcriptional corepressor, UNC-37/Groucho, which function in the VAs to block the creation of chemical synapses and gap junctions with interneurons normally reserved for VBs. To reveal downstream genes that control this choice, we have employed a cell-specific microarray strategy that has now identified unc-4-regulated transcripts. One of these genes, ceh-12, a member of the HB9 family of homeoproteins, is normally restricted to VBs. We show that expression of CEH-12/HB9 in VA motor neurons in unc-4 mutants imposes VB-type inputs. Thus, this work reveals a developmental switch in which motor neuron input is defined by differential expression of transcription factors that select alternative presynaptic partners. The conservation of UNC-4, HB9, and Groucho expression in the vertebrate motor circuit argues that similar mechanisms may regulate synaptic specificity in the spinal cord.
UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans.
Specimen part
View SamplesTumors cause the induction or repression of many genes associated with inflammation. To investigate the up and down regulation of genes associated with immune stimulation or immune tolerance RNA was isolated from dendritic cells from normal or tumor bearing prostate for microarray analysis.
FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer.
Sex, Specimen part
View SamplesTumors cause the induction or repression of many genes associated with inflammation. To investigate the up and down regulation of genes associated with immune stimulation or immune tolerance RNA was isolated from dendritic cells from normal or tumor bearing prostate for microarray analysis.
FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer.
Sex, Specimen part
View Samples