The TP53 transcription factor is frequently mutated at later stages of epithelial cancers, indicating a possible role in their invasion and metastasis. Importantly, in most cases rather than a simple loss of function p53 mutation, point mutations of p53 accumulate at the protein level and may have dominant negative functions. This study analyses gene expression differences between mice harbouring p53 mutation who do and do not develop metastasis.
Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy.
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The cohesin-associated protein Wapal is required for proper Polycomb-mediated gene silencing.
Specimen part
View SamplesThe cohesin offloading protein Wapal also acts as a polycomb factor in flies. We examined its role in transcriptional role in murine embryonic stem cells (ESCs)
The cohesin-associated protein Wapal is required for proper Polycomb-mediated gene silencing.
Specimen part
View SamplesDREAM/KChIP-3 is a calcium-dependent transcriptional repressor highly expressed in immune cells. Transgenic mice expressing a dominant active DREAM mutant show reduced serum immunoglobulin levels. In vitro assays show that reduced immunoglobulin secretion is an intrinsic defect of transgenic B cells that occurs without impairment in plasma cell differentiation but with an accelerated entry in cell division and an increase in class switch recombination. B cells from DREAM knockout mice did not show any phenotype, due to compensation by endogenous KChIP-2. Expression arrays revealed modified expression of Edem1 and Derlin3, two proteins related to the ER-associated degradation pathway and of Klf9, a cell-cycle regulator. Our results disclose a function of DREAM and KChIP-2 in Ig subclass production in B lymphocytes.
Increased B cell proliferation and reduced Ig production in DREAM transgenic mice.
Specimen part
View SamplesDREAM (downstream regulatory element antagonist modulator) is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. Previous studies have shown a role for DREAM in cerebellar function regulating the expression of the sodium/calcium exchanger3 (NCX3) in cerebellar granules to control Ca2+ homeostasis and survival of these neurons. To achieve a more global view of the genes regulated by DREAM in the cerebellum, we performed a genome-wide analysis in transgenic cerebellum expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Our results indicate that DREAM is a major transcription factor in the cerebellum that regulates genes important for cerebellar development.
Reduced Mid1 Expression and Delayed Neuromotor Development in daDREAM Transgenic Mice.
Specimen part
View SamplesDuring development a specialised subset of endothelial cells, the haemogenic endothelium, undergo an endothelial-to-haematopoietic transition. This process critically involves the transcription factor Runx1. Here we have isolated a specific subpopulation of endothelial cells using a Runx1 enhancer-reporter transgenic mouse line (23GFP). We have compared the gene expression profile of this population to non-23GFP expressing endothelial cells and CD41 expressing haematopoietic progenitor cells to assess whether 23GFP expression marks a biologically distinct subset of endothelium.
Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level.
Specimen part
View SamplesUnderstanding the mechanisms that specify neuronal subtypes is important to unravel the complex mechanisms of neuronal circuit assembly. Here we have identified a novel role for the transcription factor AP2 in progenitor and neuronal subtype specification in the cerebral cortex. Conditional deletion of AP2 causes misspecification of basal progenitors starting at
AP2gamma regulates basal progenitor fate in a region- and layer-specific manner in the developing cortex.
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