Project description:To identify genome-wide genes regulated by direct association of AMPK to chromatin in response to energy/metabolic stress, we constructed CCRF-CEM (T-ALL) stable cell lines expressing HA-AMPKα2 and performed ChIP-seq and RNA-seq assays in control or glucose deprivation conditions. ChIP-seq and RNA-seq analysis identified the histone genes as a subset of genes regulated by AMPK with direct AMPKα2 occupancy at their TSS region.
Project description:We used RNA-Seq assay to characterize AMPK-regulated gene expression patterns and then compared with EZH2-dependent transcriptional profile in MEF. We wanted to determine whether and how AMPK and EZH2 co-regulate a subset of genes.
Project description:This SuperSeries is composed of the following subset Series: GSE4063: Gene expression in skeletal muscle in AMPK gamma3 knock-out mice and wild type littermates GSE4065: Gene expression in skeletal muscle in AMPK gamma3 mutant (R225Q) transgenic mice and wild type littermates. Note: GSE4063 and GSE4065 are not directly comparable. Keywords: SuperSeries Refer to individual Series
Project description:Diacylglycerol lipase-beta (DAGLB) serves as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme regulating endocannabinoid and eicosanoid metabolism in immune cells including macrophages and dendritic cells. Genetic or pharmacological inactivation of DAGLb ameliorates inflammation and hyper-nociception in preclinical models of pathogenic pain. These beneficial effects have been assigned principally to reductions in downstream pro-inflammatory lipid signaling, leaving alternative mechanisms of regulation largely underexplored. Here, we apply quantitative chemical- and phospho-proteomics to discover that disruption of DAGLb in primary macrophages leads to LKB1-AMPK signaling activation, resulting in reprogramming of the phosphoproteome and bioenergetics. Notably, AMPK inhibition reversed the antinociceptive effects of DAGLb blockade, thereby directly supporting DAGLβ-AMPK crosstalk in vivo. Our findings uncover signaling between endocannabinoid biosynthetic enzymes and ancient energy sensing kinases to mediate cell biological and pain responses.
Project description:AMP-activated protein kinase (AMPK) is a major regulator of cellular energy homeostasis that coordinates metabolic pathways in order to balance nutrient supply with energy demand. AMPK elicits acute and diverse metabolic effects by directly phosphorylating various targets. AMPK activation also promotes metabolic reprogramming in longer term via effects on gene expression. The aim of this study is to elucidate molecular mechanism(s) by which AMPK activation modulates metabolic adaptation through its impact on gene regulation.
Project description:Diacylglycerol lipase-beta (DAGLβ) serves as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme regulating endocannabinoid and eicosanoid metabolism in immune cells including macrophages and dendritic cells. Genetic or pharmacological inactivation of DAGLβ ameliorates inflammation and hyper-nociception in preclinical models of pathogenic pain. These beneficial effects have been assigned principally to reductions in downstream proinflammatory lipid signaling, leaving alternative mechanisms of regulation largely underexplored. Here, we apply quantitative chemical- and phospho-proteomics to find that disruption of DAGLβ in primary macrophages leads to LKB1–AMPK signaling activation, resulting in reprogramming of the phosphoproteome and bioenergetics. Notably, AMPK inhibition reversed the antinociceptive effects of DAGLβ blockade, thereby directly supporting DAGLβ–AMPK crosstalk in vivo. Our findings uncover signaling between endocannabinoid biosynthetic enzymes and ancient energy-sensing kinases to mediate cell biological and pain responses.