The rising prevalence of obesity and its associated metabolic abnormalities have become global diseases that carry considerable morbidity and mortality. While there is certainly an important genetic component, extensive human epidemiologic and animal model data suggest an epigenetic component to obesity. Nevertheless, the cellular and molecular underpinnings of these pathways and how they contribute to the development of obesity remain to be elucidated. Suv420h1 and h2 are histone methyltransferases responsible for chromatin compaction and gene repression. Through in vivo, ex-vivo and in vitro studies, we found that Suv420h1 and h2 respond to environmental stimuli and regulate metabolism by downregulating PPAR-?, a master transcriptional regulator of lipid storage and glucose metabolism. Accordingly, mice lacking Suv420h proteins activate PPAR-? target genes in brown adipose tissue to increase mitochondria respiration, improve glucose tolerance and reduce adipose tissue to fight obesity. We conclude that Suv420h proteins are key epigenetic regulator of PPAR-? and the pathways controlling metabolism and weight balance in response to environmental stimuli. Overall design: For experiment 1, total RNA was isolated from males and females control- and Suv420h dKO-derived BAT. For experiment 2, total RNA was isolated from BAT collected from females control and Suv420h dKO mice after both diet regimes (nd = normal diet, hfd = high fat diet).
The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli.
Sex, Specimen part, Treatment, Subject
View SamplesResistance of Calu3 NSCLC cells to the cytotoxic nucleoside analog gemcitabine (2',2'-difluorodeoxycytidine) can be prevented as well as reversed by the rexinoid X receptor selective agonist bexarotene. This study was designed to investigate the changes in gene expression associated with gemcitabine resistance and its reversal by bexarotene. In addition to the parental Calu3 cells and the 10 cycles of treatment of the gemcitabine resistant Calu3 cells with vehicle or bexarotene, analogous treatment paradigms with gemcitabine alone as well as the combination of both compounds have been included as controls. (However, it has to be noted that in the combination treatment, cells that were re-sensitized by bexarotene have largely been removed from the culture before harvest due to the cytotoxic activity of gemcitabine.)
Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part, Treatment
View SamplesThe approval of genetically modified (GM) crops is preceded by years of intensive research to demonstrate safety to humans and environment. We recently showed that in vitro culture stress is the major factor influencing proteomic differences of GM vs. non-GM plants. This made us question the number of generations needed to erase such memory. We also wondered about the relevance of alterations promoted by transgenesis as compared to environment-induced ones.
Environmental stress is the major cause of transcriptomic and proteomic changes in GM and non-GM plants.
Specimen part
View SamplesNK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part, Treatment
View SamplesLiver RNA samples from C57BL6 mice drinking Hydrogen water for 4 weeks
Molecular hydrogen upregulates heat shock response and collagen biosynthesis, and downregulates cell cycles: meta-analyses of gene expression profiles.
Specimen part
View SamplesNK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part
View SamplesCD8+T cells are immune cells that recognize foreign antigens on infected and tumor cells, leading to cytokine-dependent expansion and activation of cytotoxicity towards the targets.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part
View SamplesCD8+T cells are immune cells that recognize foreign antigens on infected and tumor cells, leading to cytokine-dependent expansion and activation of cytotoxicity towards the targets.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part
View SamplesWe identified PDK4 as a gene with adaptive transcriptional response to chemical stress. Although PDK4 is an energy resource regulator induced by starvation, expression of other fasting-inducible genes was unaffected, indicating additional physiological role of PDK4 for liver adaptation to the chemical stress.
Adaptive gene regulation of pyruvate dehydrogenase kinase isoenzyme 4 in hepatotoxic chemical-induced liver injury and its stimulatory potential for DNA repair and cell proliferation.
Age, Specimen part
View Samples