There is differential expression of genes between cases and controls using microarray analysis, and genes that are crucial for host defence responses are significantly up-regulated in cases during pneumococcal infection.
Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case-control study.
Specimen part, Disease, Disease stage
View SamplesWe aimed to discover a combination of reliable and functionally important biomarkers of severe bacterial infection (SBI) using transcriptomics, and to evaluate their clinical validity.
Novel biomarker combination improves the diagnosis of serious bacterial infections in Malawian children.
Sex, Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Specimen part
View SamplesDOT1L as methyltransferase of H3K79 is implicated in brian development. Here, we further defined DOT1L function in gene expression during cerebellar development using Microarrays. For that we generated Dot1l knockout mice using a Atoh-Cre driver line resulting in a Dot1l knockout within the cerebellum. The RNA of cerebellar tissue of the Dot1l knockout animals was thereby compared to controls. Additionally we compared the RNA levels of cultured CGNP and CGN samples treated with a DOT1L inhibitor versus DMSO treated cells. The data sets reveals potential new gene expression targets of DOT1L in vivo and in vitro, which ensure a correct development of the cerebellum.
Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Specimen part
View Samplesp63 mutations have been associated with several human hereditary disorders characterized by ectodermal dysplasia such as EEC syndrome, ADULT syndrome and AEC syndrome . The location and functional effects of the mutations that underlie these syndromes reveal a striking genotype-phenotype correlation. Unlike EEC and ADULT that result from missense mutations in the DNA-binding domain of p63, AEC is solely caused by missense mutations in the SAM domain of p63. We report a study on the TAp63a isoform, the first to be expressed during development of the embryonic epithelia, and on its naturally occurring Q540L mutant derived from an AEC patient. To assess the effects of the Q540L mutation, we generated stable cell lines expressing TAp63a wt, DeltaNp63 alpha or the TAp63 alpha-Q540L mutant protein and used them to systematically compare the cell growth regulatory activity of the mutant and wt p63 proteins and to generate, by microarray analysis, a comprehensive profile of differential gene expression. We found that the Q540L substitution impairs the transcriptional activity of TAp63a and causes misregulation of genes involved in the control of cell growth and epidermal differentiation.
The Hay Wells syndrome-derived TAp63alphaQ540L mutant has impaired transcriptional and cell growth regulatory activity.
No sample metadata fields
View SamplesGenome-wide association studies (GWAS) have identified dozens of genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the biological functions of these common genetic variants and the mechanisms to increase disease risk are largely unknown. We integrated chromatin-IP coupled sequencing (ChIP-seq) and microarray expression profiling in the TMPRSS2-ERG gene rearrangement positive DuCaP cell model with the NHGRI GWAS PCa risk SNPs catalog, in an attempt to identify disease susceptibility SNPs localized within functional androgen receptor binding sites (ARBSs). Among the 48 GWAS index SNPs and 2,702 linked SNPs defined by the 1000G project 104 were found to be localized in the AR ChIP-seq peaks. Of these risk SNPs, rs11891426 T/G in the 7th intron of its host gene melanophilin (MLPH) was found located within a putative auxiliary ARE motif, which we found enriched in the neighborhood of canonical ARE motifs. Exchange of T to G attenuated the transcriptional activity of the MLPH-ARBS in a reporter gene assay. The expression of MLPH protein in tissue samples from prostate cancer patients was significantly lower in those with the G compared to the T allele. Moreover, a significant positive correlation of AR and MLPH protein expression levels was also confirmed in tissue samples. These results unravel a hidden link between AR and a functional PCa risk SNP rs11891426, whose allele alteration affects androgen regulation of its host gene MLPH. This study shows the power of integrative studies to pin down functional risk SNPs and justifies further investigations.
Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.
Cell line, Treatment, Time
View SamplesOchratoxin A gene expression profiling in liver and kidney, with time points of exposure from 7 days to 12 motnhs
A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
Cell line, Time
View SamplesBTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements (MAREs) at low intracellular heme levels. Upon heme binding, BACH1 is released from the MAREs, resulting in increased expression of antioxidant response genes. To systematically address the gene regulatory networks involving BACH1, we performed knock-down of BACH1 in HEK 293T cells using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays.
The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
Cell line, Time
View SamplesWe have studied the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by binding to promoters as well as TSS-distal enhancer regions. In contrast to flies, the MSL complex is not enriched on the X chromosome yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix ncRNA, the major repressor of Xist lncRNA. MSL depletion leads to severely decreased Tsix expression, reduced REX1 recruitment, and consequently accumulation of Xist RNA in ESCs. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs. Overall design: We have performed ChIP-seq of KANSL3, MCRS1, MOF, MSL1 and MSL2 in mouse ESCs, and KANSL3, MOF and MSL2 in NPCs, in duplicate and normalised against their inputs. We have also performed RNA-seq following knockdown of Kansl3, Mof, Msl1 and Msl2 mouse embryonic stem cells in triplicate. NB: Kansl3 and Mof knockdown-RNAseq are analyzed against their own scrambled controls, and Msl1 and Msl2 against another scrambled control triplicate. siMCRS1 & siMOF were compared to scrambled1 (scr1) siMsl1 and siMsl2 were compared to scr2 siNsl3 was compared to scr3
MOF-associated complexes ensure stem cell identity and Xist repression.
No sample metadata fields
View Samples