Genome wide gene expression analysis in G9a knockdown myoblasts
G9a promotes proliferation and inhibits cell cycle exit during myogenic differentiation.
Specimen part
View SamplesThere is a continuing need for driver strains to enable cell type-specific manipulation in the nervous system. Each cell type expresses a unique set of genes, and recapitulating expression of marker genes by BAC transgenesis or knock-in has generated useful transgenic mouse lines. However since genes are often expressed in many cell types, many of these lines have relatively broad expression patterns. We report an alternative transgenic approach capturing distal enhancers for more focused expression. We identified an enhancer trap probe often producing restricted reporter expression and developed efficient enhancer trap screening with the PiggyBac transposon. We established more than 200 lines and found many lines that label small subsets of neurons in brain substructures, including known and novel cell types. Images and other information about each line are available online (http://enhnacertrap.bio.brandeis.edu). Overall design: Examination of 6 cortical mouse neuronal cell types. 5 of which are in layer 6 in 3 different cortical regions.
A Mammalian enhancer trap resource for discovering and manipulating neuronal cell types.
Sex, Cell line, Subject
View SamplesThe androgen receptor (AR) directs diverse biological processes through interaction with coregulators such as androgen receptor trapped clone-27 (ART-27). The impact of ART-27 on genome-wide transcription was examined. The studies indicate that loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression. Surprisingly, classes of genes that are upregulated upon ART-27 depletion include regulators of DNA damage checkpoint and cell cycle progression, suggesting that ART-27 functions to keep expression levels of these genes low.
Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells.
Sex, Specimen part
View SamplesGene expression in forebrain structures change during day and night depending on circadian and rest-activity cycles. Clock genes have been shown to be involved in the control of circadian and sleep-wake control.
Mice lacking the circadian modulators SHARP1 and SHARP2 display altered sleep and mixed state endophenotypes of psychiatric disorders.
Age, Specimen part, Time
View SamplesThe cytokines GM-CSF and IL-5 are thought to possess largely divergent functions despite a shared dependence on the common beta (βC) chain to initiate signaling. Although IL-5 is part of the core type 2 cytokine signature and is required for protection against some helminths, it is dispensable for immunity to others, such as Heligmosomoides polygyrus bakeri (H. polygyrus). Whether this is due to compensatory mechanisms is unclear. The transcription factor Bhlhe40 has been shown to control GM-CSF production and is proposed to be a novel regulator of T helper type 2 cells.
BHLHE40 Promotes T<sub>H</sub>2 Cell-Mediated Antihelminth Immunity and Reveals Cooperative CSF2RB Family Cytokines.
Sex, Specimen part, Treatment
View SamplesMicroarray data on TH cell subsets from WT C57BL/6 and Bhlhe40 KO mice
Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation.
Specimen part, Treatment
View SamplesHuntingtons Disease (HD) is an inherited neurodegenerative disease caused by a glutamine repeat expansion in huntingtin protein. Transcriptional deregulation and altered energy metabolism have been implicated in HD pathogenesis. We report here that mutant huntingtin causes disruption of mitochondrial function by inhibiting expression of PGC-1a, a transcriptional coactivator that regulates several metabolic processes including mitochondrial biogenesis and respiration. Mutant huntingtin represses PGC-1a gene transcription by associating with the promoter and interfering with the CREB/TAF4-dependent transcriptional pathway critical for the regulation of PGC-1a gene expression. Crossbreeding of PGC-1a knockout mice with HD knock-in mice leads to increased neurodegeneration of striatal neurons and motor abnormalities in the HD mice. Importantly, expression of PGC-1a partially reverses the toxic effects of mutant huntingtin in cultured striatal neurons. Moreover, lentiviral-mediated delivery of PGC-1a in the striatum provides neuroprotection in the transgenic HD mice. These studies suggest a key role for PGC-1a in the control of energy metabolism in the early stages of HD pathogenesis.
Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration.
Sex, Age, Specimen part
View SamplesFibroadenomas are the most common benign breast tumors in women under 30. Unlike their malignant counterparts, relatively molecular profiling has been done on fibroadenomas. Here we performed gene expression profiling on ten fibroadenomas in order to better characterize these tumors. Through targeted amplicon sequencing, we have found that six of these tumors have MED12 mutations. We show that the MED12 mutations, among others, are associated with activated estrogen signaling, as well as increased invasiveness through upregulation of ECM remodelling genes.
Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.
Age
View SamplesThe Spt4-Spt5 complex, and its human homolog DSIF (DRB sensitivity-inducing factor), is unique in its ability to regulate Pol II processivity. Previous studies have shown that Spt5 has the characteristics of a general transcription-elongation factor. However, mutagenesis of Spt5 showed specific phenotypes during development, which were far less severe than those of Pol II defects or TBP deficient embryos. It seems paradoxical that a mutation which alters a general elongation factor can cause rather specific developmental defects. By using Spt5 knockdown zebrafish embryos and microarrays, here we showed that transcript abundance for only a small subset of genes is altered by loss of Spt5. Further investigation of the down-regulated genes showed that the genes most intensely repressed by the knockdown were strongly activated during early development in untreated embryos. Thus, this study shows that gene activation levels may create different requirements for Pol II processivity. Active transcription requires Spt5 for efficient elongation through its stimulatory activity on Pol II processivity.
Erythropoiesis is regulated by the transcription elongation factor Foggy/Spt5 through gata1 gene regulation.
Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer.
Sex, Age
View Samples