KRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule. KRAP-deficient (KRAP-/-) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP-/- mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia.
Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice.
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View SamplesKRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule. KRAP-deficient (KRAP-/-) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP-/- mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia.
Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice.
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View SamplesEpigenetic modifications must underlie lineage-specific differentiation since terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Hematopoiesis provides a well-defined model of progressive differentiation in which to study the role of epigenetic modifications in cell fate decisions. Multi-potent progenitors (MPPs) can differentiate into all blood cell lineages, while downstream progenitors commit to either myeloerythroid or lymphoid lineages. While DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs {Broske, 2009 #6}, a comprehensive DNA methylation map of hematopoietic progenitors, or of any cell lineage, does not exist. Here we have generated a mouse DNA methylation map, examining 4.6 million CpG sites throughout the genome including all CpG islands and shores, examining MPPs, all lymphoid progenitors (ALPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Interestingly, differentiation towards the myeloid lineage corresponds with a net decrease in DNA methylation, while lymphoid commitment involves a net increase in DNA methylation, but both show substantial dynamic changes consistent with epigenetic plasticity during development. By comparing lineage-specific DNA methylation to gene expression array data, we find many examples of genes and pathways not previously known to be involved in lymphoid/myeloid differentiation, such as Gcnt2, Arl4c, Gadd45, and Jdp2. Several transcription factors, including Meis1 and Prdm16 were methylated and silenced during differentiation, suggesting a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome appears to be important in hematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation, often correlating with gene expression changes, and define a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions.
Comprehensive methylome map of lineage commitment from haematopoietic progenitors.
Sex, Age
View SamplesThis array set was used to identify the genes that are highly expressed in the mouse suprachiasmatic nucleus (SCN). Because pharmacological inhibition of Gai/o activity with pertussis toxin hampers intercellular synchronization and causes dampened rhythms of the entire SCN, we hypothesized that member(s) of the Regulator of G protein Signaling (RGS) family might contribute to synchronized cellular oscillations in the SCN. To test this hypothesis, we surveyed all known mouse Rgs genes for their expression by using GeneChip and selected the genes that are highly expressed in the SCN for further analysis.
Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus.
Sex, Age, Specimen part, Disease, Treatment, Time
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