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Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels [lxr_chip]

ABSTRACT: Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels [lxr_chip]

PROVIDER: PRJNA1016296 | ENA |

REPOSITORIES: ENA

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Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels [lxr_chip]

Project description:Transitions from a fed to a fasted state are common in mammals. The liver orchestrates adaptive responses to feeding/fasting by transcriptionally regulating metabolic pathways of energy usage and storage. Transcriptional and enhancer dynamics following cessation of fasting (refeeding) were never explored. We aimed to inspect the transcriptional and chromatin events occurring upon refeeding, their kinetic behavior and their molecular drivers. We found that the refeeding response is temporally-organized with an early response focused on ramping up protein translation while later stages of refeeding drive a bifurcated lipid synthesis program. While both lipid synthesis pathways were inhibited during fasting, cholesterol biosynthesis genes returned to their basal levels upon refeeding while lipogenesis genes significantly overshoot above pre-fasting levels. Lipogenic gene overshoot is dictated by Liver X Receptor alpha (LXRα) which directly binds and activates lipogenic enhancers. These findings unravel the mechanism behind the long-known phenomenon of refeeding fat overshoot.

2024-07-10 | GSE243051 | GEO

Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels [lxr_atac]

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Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels [kinetics_rna]

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Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels [lxr_rna]

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Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels

Project description:Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels

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LXR-dependent enhancer activation regulates the temporal organization of the liver's response to refeeding leading to lipogenic gene overshoot

Project description:Transitions between the fed and fasted state are common in mammals. The liver orchestrates adaptive responses to feeding/fasting by transcriptionally regulating metabolic pathways of energy usage and storage. Transcriptional and enhancer dynamics following cessation of fasting (refeeding) have not been explored. We examined the transcriptional and chromatin events occurring upon refeeding in mice, including kinetic behavior and molecular drivers. We found that the refeeding response is temporally-organized with the early response focused on ramping up protein translation while the later stages of refeeding drive a bifurcated lipid synthesis program. While both the cholesterol biosynthesis and lipogenesis pathways were inhibited during fasting, most cholesterol biosynthesis genes returned to their basal levels upon refeeding while most lipogenesis genes markedly overshoot above pre-fasting levels. Gene knockout, enhancer dynamics and ChIP-seq analyses revealed that lipogenic gene overshoot is dictated by LXRα. These findings from unbiased analyses unravel the mechanism behind the long-known phenomenon of refeeding fat overshoot.

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Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels

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

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