Alterations in promoter interaction landscape and transcriptional network underlying metabolic adaptation to diet

Yufeng Qin, Sara A. Grimm, John D. Roberts, Kaliopi Chrysovergis and Paul A. Wade ()
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Yufeng Qin: National Institute of Environmental Health Sciences
Sara A. Grimm: National Institute of Environmental Health Sciences
John D. Roberts: National Institute of Environmental Health Sciences
Kaliopi Chrysovergis: National Institute of Environmental Health Sciences
Paul A. Wade: National Institute of Environmental Health Sciences

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Metabolic adaptation to nutritional state requires alterations in gene expression in key tissues. Here, we investigated chromatin interaction dynamics, as well as alterations in cis-regulatory loci and transcriptional network in a mouse model system. Chronic consumption of a diet high in saturated fat, when compared to a diet high in carbohydrate, led to dramatic reprogramming of the liver transcriptional network. Long-range interaction of promoters with distal regulatory loci, monitored by promoter capture Hi-C, was regulated by metabolic status in distinct fashion depending on diet. Adaptation to a lipid-rich diet, mediated largely by nuclear receptors including Hnf4α, relied on activation of preformed enhancer/promoter loops. Adaptation to carbohydrate-rich diet led to activation of preformed loops and to de novo formation of new promoter/enhancer interactions. These results suggest that adaptation to nutritional changes and metabolic stress occurs through both de novo and pre-existing chromatin interactions which respond differently to metabolic signals.

Date: 2020
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DOI: 10.1038/s41467-020-14796-x

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