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Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans

ABSTRACT: Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans

PROVIDER: PRJNA521021 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8531020.fastq.gz	Fastqsanger.gz
	SRR8531030.fastq.gz	Fastqsanger.gz
	SRR8531040_1.fastq.gz	Fastqsanger.gz
	SRR8531040_2.fastq.gz	Fastqsanger.gz
	SRR8531050_1.fastq.gz	Fastqsanger.gz

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Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans [cHiC-seq]

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Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans [RNA-seq]

Project description:Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors, and characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority is located in non-coding DNA regions. This suggest that most variants mediate their effect by altering the activity of gene-regulatory elements, including enhancers. Here, we map skeletal muscle genomic enhancer elements that are dynamically regulated after exposure to the free fatty acid palmitate or the inflammatory cytokine TNFα. By overlapping enhancer positions with the location of disease-associated genetic variants, and resolving long-range chromatin interactions between enhancers and gene promoters, we identify target genes involved in metabolic dysfunction in skeletal muscle. The majority of these genes also associate with altered whole-body metabolic phenotypes in the murine BXD genetic reference population. Thus, our combined genomic investigations identified genes that are involved in skeletal muscle metabolism and linked to SNPs associated with the development of obesity and T2D.

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Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans [cHiC-seq]

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Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans

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

2020-03-26 | GSE126102 | GEO

Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism.

Project description:Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority are located in non-coding DNA regions. This suggests that most variants mediate their effect by altering the activity of gene-regulatory elements, including enhancers. Here, we map skeletal muscle genomic enhancer elements that are dynamically regulated after exposure to the free fatty acid palmitate or the inflammatory cytokine TNFα. By overlapping enhancer positions with the location of disease-associated genetic variants, and resolving long-range chromatin interactions between enhancers and gene promoters, we identify target genes involved in metabolic dysfunction in skeletal muscle. The majority of these genes also associate with altered whole-body metabolic phenotypes in the murine BXD genetic reference population. Thus, our combined genomic investigations identified genes that are involved in skeletal muscle metabolism.

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Reverse gene-environment interaction approach to identify variants influencing body mass index in humans

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Regulation of skeletal muscle energy/nutrient-sensing pathways during metabolic adaptation to fasting in healthy humans

Project description:The aim of the study was to investigate how short-term fasting affects whole-body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, twelve young healthy men were studied during a 24-hour fast. Skeletal muscle biopsies were collected and analyzed at baseline and after 4, 10 and 24h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose towards lipid oxidation. Transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time-points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle

2014-12-02 | GSE55924 | GEO

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