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Article
Open AccessMyeloid-derived miR-6236 potentiates adipocyte insulin signaling and prevents hyperglycemia during obesity
Adipose tissue macrophages (ATMs) influence obesity-associated metabolic dysfunction, but the mechanisms by which they do so are not well understood. We show that miR-6236 is a bona fide miRNA that is secreted...
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Article
Nuclear receptor corepressors non-canonically drive glucocorticoid receptor-dependent activation of hepatic gluconeogenesis
Nuclear receptor corepressors (NCoRs) function in multiprotein complexes containing histone deacetylase 3 (HDAC3) to alter transcriptional output primarily through repressive chromatin remodelling at target loci1
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Article
Open AccessAuthor Correction: Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice
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Article
Open AccessCardiomyocyte-specific disruption of the circadian BMAL1–REV-ERBα/β regulatory network impacts distinct miRNA species in the murine heart
Circadian disruption increases cardiovascular disease (CVD) risk, through poorly understood mechanisms. Given that small RNA species are critical modulators of cardiac physiology/pathology, we sought to determ...
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Article
Open AccessMicroglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice
Alzheimer’s disease, the most common age-related neurodegenerative disease, is characterized by tau aggregation and associated with disrupted circadian rhythms and dampened clock gene expression. REV-ERBα is a...
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Article
Modelling metabolic diseases and drug response using stem cells and organoids
Metabolic diseases, including obesity, diabetes mellitus and cardiovascular disease, are a major threat to health in the modern world, but efforts to understand the underlying mechanisms and develop rational t...
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Article
Circadian REV-ERBs repress E4bp4 to activate NAMPT-dependent NAD+ biosynthesis and sustain cardiac function
The heart is a highly metabolic organ that uses multiple energy sources to meet its demand for ATP production. Diurnal feeding–fasting cycles result in fluctuations in substrate availability, which, together w...
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Using GRO-Seq to Measure Circadian Transcription and Discover Circadian Enhancers
Circadian gene transcription transmits timing information and drives cyclic physiological processes across various tissues. Recent studies indicate that oscillating enhancer activity is a major driving force o...
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Article
Dichotomous engagement of HDAC3 activity governs inflammatory responses
The histone deacetylases (HDACs) are a superfamily of chromatin-modifying enzymes that silence transcription through the modification of histones. Among them, HDAC3 is unique in that interaction with nuclear r...
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Article
Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity
Quantitative changes in leptin concentration lead to alterations in food intake and body weight, but the regulatory mechanisms that control leptin gene expression are poorly understood. Here we report that fat...
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Article
Integrative regulation of physiology by histone deacetylase 3
Cell-type-specific gene expression is physiologically modulated by the binding of transcription factors to genomic enhancer sequences, to which chromatin modifiers such as histone deacetylases (HDACs) are recr...
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Article
Open AccessAn HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides
The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cr...
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Article
Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge
Histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude.
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Article
Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3 depletion
Genetic deletion of HDAC3, a circadian epigenome regulator, specifically in skeletal muscle alters amino acid metabolism, leading to increased muscle endurance but at the cost of whole-body insulin resistance.
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Article
Genetic and epigenomic mechanisms of mammalian circadian transcription
In this Review, the authors consider the functions of key clock transcription factors and the epigenetic regulatory mechanisms that direct circadian gene expression in mammalian cells.
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Article
Nutrient-sensing nuclear receptors coordinate autophagy
The nuclear receptors FXR and PPARα are shown to regulate autophagy by competing for binding to shared sites in the promoters of autophagic genes; in the fed state FXR suppresses hepatic autophagy, whereas in ...
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Article
Open AccessLC-MS and GC-MS based metabolomics platform for cancer research
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Article
Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis
This work identifies a role for intestinal epithelial cell (IEC)-intrinsic expression of histone deacetylase 3 in regulating commensal-bacteria-dependent gene expression and intestinal homeostasis; IEC-specifi...
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Article
Open AccessMetabolite and transcriptome analysis during fasting suggest a role for the p53-Ddit4 axis in major metabolic tissues
Fasting induces specific molecular and metabolic adaptions in most organisms. In biomedical research fasting is used in metabolic studies to synchronize nutritional states of study subjects. Because there is a...
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Article
The nuclear receptor Rev-erbα controls circadian thermogenic plasticity
The nuclear receptor Rev-erbα, a powerful repressor of transcription, is shown to link circadian and thermogenic networks by regulating the function of brown adipose tissue.
