This SuperSeries is composed of the SubSeries listed below.
Double-stranded microRNA mimics can induce length- and passenger strand-dependent effects in a cell type-specific manner.
Cell line
View SamplesExperiment 1 - miR-155 and miR-199 Phenotype
Double-stranded microRNA mimics can induce length- and passenger strand-dependent effects in a cell type-specific manner.
Cell line
View SamplesExperiment 2 - MiRNA mimics have a length and passenger strand specific effect
Double-stranded microRNA mimics can induce length- and passenger strand-dependent effects in a cell type-specific manner.
Cell line
View SamplesThe histone deacetylase HDAC2, which negatively regulates neuronal plasticity and synaptic gene expression, is upregulated both in Alzheimer’s disease (AD) patients and mouse models (Graff et al., 2012). Therapeutics targeting HDAC2 are speculated to be a promising avenue for ameliorating AD related cognitive impairment. However, attempts to generate HDAC2-specific inhibitors have not been successful. Here, we take a novel approach utilizing integrative genomics to identify proteins that mediate HDAC2 recruitment to synaptic plasticity genes. Functional screening revealed that knockdown of the transcription factor Sp3 phenocopied HDAC2 knockdown, and that Sp3 facilitated the recruitment of HDAC2 to synaptic genes. Importantly, like HDAC2, Sp3 expression was elevated in AD patients and mouse models, where Sp3 knockdown ameliorated synaptic dysfunction. Furthermore, exogenous expression of an HDAC2 fragment containing the Sp3 binding domain fully restored synaptic plasticity and memory in a mouse model with severe neurodegeneration. Our findings indicate that targeting the HDAC2-Sp3 complex could enhance synaptic and cognitive function, without affecting HDAC2 function in other processes. Overall design: We profiled gene expression levels in primary neurons treated with HDAC2 or Sp3 shRNAs through RNA-Seq to examine whether HDAC2 and Sp3 cooperatively regulate a set of genes.
The Transcription Factor Sp3 Cooperates with HDAC2 to Regulate Synaptic Function and Plasticity in Neurons.
Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Master regulators of FGFR2 signalling and breast cancer risk.
Specimen part, Cell line
View SamplesGenome-wide association studies for breast cancer have identified over 80 different risk regions in the genome, with the FGFR2 locus consistently identified as the most strongly associated locus. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Here we use a systems biology approach to elucidate the regulatory networks operating in breast cancer and examine the role of FGFR2 in mediating risk. Using model systems we identify FGFR2-regulated genes and, combining variant set enrichment and eQTL analysis, show that these are preferentially linked to breast cancer risk loci. Our results support the concept that cancer-risk associated genes cluster in pathways
Master regulators of FGFR2 signalling and breast cancer risk.
Cell line
View SamplesGenome-wide association studies for breast cancer have identified over 80 different risk regions in the genome, with the FGFR2 locus consistently identified as the most strongly associated locus. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Here we use a systems biology approach to elucidate the regulatory networks operating in breast cancer and examine the role of FGFR2 in mediating risk. Using model systems we identify FGFR2-regulated genes and, combining variant set enrichment and eQTL analysis, show that these are preferentially linked to breast cancer risk loci. Our results support the concept that cancer-risk associated genes cluster in pathways
Master regulators of FGFR2 signalling and breast cancer risk.
Cell line
View SamplesGenome-wide association studies for breast cancer have identified over 80 different risk regions in the genome, with the FGFR2 locus consistently identified as the most strongly associated locus. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Here we use a systems biology approach to elucidate the regulatory networks operating in breast cancer and examine the role of FGFR2 in mediating risk. Using model systems we identify FGFR2-regulated genes and, combining variant set enrichment and eQTL analysis, show that these are preferentially linked to breast cancer risk loci. Our results support the concept that cancer-risk associated genes cluster in pathways
Master regulators of FGFR2 signalling and breast cancer risk.
Cell line
View SamplesGenome-wide association studies for breast cancer have identified over 80 different risk regions in the genome, with the FGFR2 locus consistently identified as the most strongly associated locus. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Here we use a systems biology approach to elucidate the regulatory networks operating in breast cancer and examine the role of FGFR2 in mediating risk. Using model systems we identify FGFR2-regulated genes and, combining variant set enrichment and eQTL analysis, show that these are preferentially linked to breast cancer risk loci. Our results support the concept that cancer-risk associated genes cluster in pathways
Master regulators of FGFR2 signalling and breast cancer risk.
Specimen part
View SamplesConditional knockout of the transcription factor Ronin (Thap11) in retinal progenitor cells (RPCs) results in a profound failure cell proliferation resulting in a hypoplastic adult retina that also suffers from photoreceptor degeneration. The goal of this study was to determine which genes are deregulated in response to loss of Ronin transcription factor activity in the developing retina. We generated Ronin flox/flox (Control) and Chx10-Cre::GFP+/tg; Ronin flox/flox (CKO) mice, in which Ronin loss occurs specifically within RPCs, and performed RNA-Seq analysis of embryonic day E14.5 (E14.5) retinae. Three independent pools of control and Ronin CKO retinae were collected consisting of a minimum of 10 retinae per pool and total RNA was extracted followed by polyA selection, fractionation (200-500 nucleotide range) and generation of cDNA. The resulting DNA was then used for standard Illumina adaptor ligation and sequencing. This experiment revealed decreased expression of a large group of mitochondrial genes including components of the electron transport chain (ETC), which have been recently implicated as direct regulators of the cell cycle. Overall design: Retinal mRNA profiles of embryonic day 14.5 (E14.5) Control (Ronin flox/flox) and Ronin CKO (Chx10-Cre::GFP+/tg; Ronin flox/flox) mice were generated by deep sequencing, in triplicate using Illumina HiSeq2500
RONIN Is an Essential Transcriptional Regulator of Genes Required for Mitochondrial Function in the Developing Retina.
Specimen part, Subject
View Samples