Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism
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Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism. / Williams, Kristine; Ingerslev, Lars Roed; Bork-Jensen, Jette; Wohlwend, Martin; Hansen, Ann Normann; Small, Lewin; Ribel-Madsen, Rasmus; Astrup, Arne; Pedersen, Oluf Borbye; Auwerx, Johan; Workman, Christopher T; Grarup, Niels; Hansen, Torben; Barrès, Romain.
I: Nature Communications, Bind 11, 2695, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism
AU - Williams, Kristine
AU - Ingerslev, Lars Roed
AU - Bork-Jensen, Jette
AU - Wohlwend, Martin
AU - Hansen, Ann Normann
AU - Small, Lewin
AU - Ribel-Madsen, Rasmus
AU - Astrup, Arne
AU - Pedersen, Oluf Borbye
AU - Auwerx, Johan
AU - Workman, Christopher T
AU - Grarup, Niels
AU - Hansen, Torben
AU - Barrès, Romain
N1 - CURIS 2020 NEXS 179
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-16537-6
DO - 10.1038/s41467-020-16537-6
M3 - Journal article
C2 - 32483258
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2695
ER -
ID: 242605984