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Characterization of chromatin and gene expression changes during fasting and refeeding in mouse liver [ChIP-Seq]

ABSTRACT: Characterization of chromatin and gene expression changes during fasting and refeeding in mouse liver [ChIP-Seq]

PROVIDER: PRJNA636604 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11892157.fastq.gz	Fastqsanger.gz
	SRR11892158.fastq.gz	Fastqsanger.gz
	SRR11892159.fastq.gz	Fastqsanger.gz
	SRR11892160.fastq.gz	Fastqsanger.gz
	SRR11892161.fastq.gz	Fastqsanger.gz

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Characterization of chromatin and gene expression changes during fasting and refeeding in mouse liver [ChIP-Seq]

Project description:The discovery of FoxO1 as an effector of insulin action on gene expression filled a gap in our knowledge of insulin signaling. The metabolic impact of hepatic FoxO1 has been demonstrated in genetic mouse models showing that FoxO1 inhibition can reverse diabetes. However, the gamut of FoxO1 targets is unknown, due to the lack of robust genome-wide chromatin occupancy data. To elucidate the genomic architecture of the FoxO1 effect on liver metabolism, we integrated genome-wide ChIP-seq and RNA-seq. During the physiological transition from fasting to refeeding, hepatic FoxO1 translocated from the nucleus to the cytoplasm. At the same time points, cistrome analysis demonstrated that 60% of FoxO1 target sites were cleared by refeeding. RNA-seq from mice following acute liver-specific FoxO1 ablation allowed us to integrate the data in a comprehensive FoxO1 regulome. We identified four distinct classes of FoxO1 targets. Class I targets are enriched in genes regulating cell homeostasis, have FoxO1 sites clustered in promoters and do not show regulation with fasting/refeeding. Class II is comprised of canonical FoxO1 metabolic targets coordinately regulated with other fasting-inducible TFs, such as PPARA, CREB, and GR through promoters. Class III is enriched in glucose metabolic genes regulated through active enhancers, as detected by H3K4me1 and H3K27ac histone marks. Class IV is comprised of triglyceride (TG) and lipoprotein metabolism genes, regulated through intron sites, and characterized by an uneven response to fasting/refeeding regulation.

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Characterization of chromatin and gene expression changes during fasting and refeeding in mouse liver [RNA-Seq]

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Characterization of chromatin and gene expression changes during fasting and refeeding in mouse liver

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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]

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.

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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]

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Characterization of chromatin and gene expression changes during fasting and refeeding in mouse liver [RNA-Seq]

Project description:Characterization of chromatin and gene expression changes during fasting and refeeding in mouse liver [RNA-Seq]

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Project description:Gene expression profile was investigated using zebrafish muscle unger fasting-refeeding conditions. This study revealed fasting-refeeding responsive genes in zebrafish muscle.

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