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Clockwork orange-mediated control of sugar responsive transcription

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Drosophila melanogaster

PROVIDER: GSE207199 | GEO | 2023/06/01

REPOSITORIES: GEO

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Clockwork orange-mediated control of sugar responsive transcription [cwo mutant]

Project description:Feeding on high sugar diet reprograms metabolism, partially mediated through a gene regulatory network controlled by intracellular sugar sensor Mondo/ChREBP-Mlx. Sugar-induced gene expression changes include activation of genes encoding enzymes of glycolysis, pentose phosphate pathways, and de novo lipogenesis, collectively driving the flux of sugar-derived carbon into triacylglycerides. These sugar-induced metabolic changes are likely to trigger compensatory responses to avoid depletion of necessary metabolites, but they remain poorly characterized. Through a global temporal clustering analysis of sugar-induced gene expression in Drosophila we identify new gene expression programs controlled by sugar feeding. These include rapid and transient downregulation of ribosome biogenesis genes, known targets of transcription factor Myc. Through in silico motif predictions and experimental validation, we identify transcriptional repressor Clockwork orange (CWO) as a mediator of this response. CWO expression is directly activated by Mondo-Mlx and it counteracts Myc through repression of its expression as well as through binding to overlapping regulatory regions of ribosome biogenesis genes. Loss of CWO function leads to depletion of UDP-GlcNAc pools and impaired viability on high sugar diet. Analysis of CWO orthologs, BHLHE40 and BHLHE41, in mouse hepatocytes revealed a conserved role for BHLHE41 in repressing ribosome biogenesis genes. Collectively, our data uncover a gene regulatory circuit balancing the activities of lipid and protein biosynthesis to maintain homeostasis during high sugar feeding.

2023-06-01 | GSE207196 | GEO

Clockwork orange-mediated control of sugar responsive transcription [ChIP-seq]

2023-06-01 | GSE207198 | GEO

Clockwork orange-mediated control of sugar responsive transcription [time series]

2023-06-01 | GSE207197 | GEO

Clockwork orange-mediated control of sugar responsive transcription

Project description:Clockwork orange-mediated control of sugar responsive transcription

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Clockwork orange-mediated control of sugar responsive transcription [cwo mutant]

Project description:Clockwork orange-mediated control of sugar responsive transcription [cwo mutant]

| PRJNA854147 | ENA

Clockwork orange-mediated control of sugar responsive transcription [time series]

Project description:Clockwork orange-mediated control of sugar responsive transcription [time series]

| PRJNA854146 | ENA

Clockwork orange-mediated control of sugar responsive transcription [ChIP-seq]

Project description:Clockwork orange-mediated control of sugar responsive transcription [ChIP-seq]

| PRJNA854144 | ENA

Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component

Project description:This SuperSeries is composed of the SubSeries listed below.

2007-07-09 | GSE8391 | GEO

CLOCKWORK ORANGE promotes CLOCK-CYCLE activation via the putative Drosophila ortholog of CLOCK INTERACTING PROTEIN CIRCADIAN

Project description:This SuperSeries is composed of the SubSeries listed below.

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High intake of dietary sugar enhances bisphenol A (BPA) disruption and reveals ribosome-mediated pathways of toxicity

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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