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


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 Hnf4?, 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.

SUBMITTER: Qin Y 

PROVIDER: S-EPMC7031266 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Qin Yufeng Y   Grimm Sara A SA   Roberts John D JD   Chrysovergis Kaliopi K   Wade Paul A PA  

Nature communications 20200219 1


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 prom  ...[more]

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