In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 7 ( 2023-7-21), p. e3002192-
Abstract:
During exercise, skeletal muscle is exposed to a low oxygen condition, hypoxia. Under hypoxia, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is stabilized and induces expressions of its target genes regulating glycolytic metabolism. Here, using a skeletal muscle-specific gene ablation mouse model, we show that Brg1/Brm-associated factor 155 (Baf155), a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, is essential for HIF-1α signaling in skeletal muscle. Muscle-specific ablation of Baf155 increases oxidative metabolism by reducing HIF-1α function, which accompanies the decreased lactate production during exercise. Furthermore, the augmented oxidation leads to high intramuscular adenosine triphosphate (ATP) level and results in the enhancement of endurance exercise capacity. Mechanistically, our chromatin immunoprecipitation (ChIP) analysis reveals that Baf155 modulates DNA-binding activity of HIF-1α to the promoters of its target genes. In addition, for this regulatory function, Baf155 requires a phospho-signal transducer and activator of transcription 3 (pSTAT3), which forms a coactivator complex with HIF-1α, to activate HIF-1α signaling. Our findings reveal the crucial role of Baf155 in energy metabolism of skeletal muscle and the interaction between Baf155 and hypoxia signaling.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002192
DOI:
10.1371/journal.pbio.3002192.g001
DOI:
10.1371/journal.pbio.3002192.g002
DOI:
10.1371/journal.pbio.3002192.g003
DOI:
10.1371/journal.pbio.3002192.g004
DOI:
10.1371/journal.pbio.3002192.g005
DOI:
10.1371/journal.pbio.3002192.g006
DOI:
10.1371/journal.pbio.3002192.g007
DOI:
10.1371/journal.pbio.3002192.g008
DOI:
10.1371/journal.pbio.3002192.s001
DOI:
10.1371/journal.pbio.3002192.s002
DOI:
10.1371/journal.pbio.3002192.s003
DOI:
10.1371/journal.pbio.3002192.s004
DOI:
10.1371/journal.pbio.3002192.s005
DOI:
10.1371/journal.pbio.3002192.s006
DOI:
10.1371/journal.pbio.3002192.s007
DOI:
10.1371/journal.pbio.3002192.s008
DOI:
10.1371/journal.pbio.3002192.s009
DOI:
10.1371/journal.pbio.3002192.s010
DOI:
10.1371/journal.pbio.3002192.s011
DOI:
10.1371/journal.pbio.3002192.s012
DOI:
10.1371/journal.pbio.3002192.s013
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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