First Author | Kang JS | Year | 2023 |
Journal | PLoS Biol | Volume | 21 |
Issue | 7 | Pages | e3002192 |
PubMed ID | 37478146 | Mgi Jnum | J:346278 |
Mgi Id | MGI:7515808 | Doi | 10.1371/journal.pbio.3002192 |
Citation | Kang JS, et al. (2023) Baf155 regulates skeletal muscle metabolism via HIF-1a signaling. PLoS Biol 21(7):e3002192 |
abstractText | During exercise, skeletal muscle is exposed to a low oxygen condition, hypoxia. Under hypoxia, the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) 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-1alpha signaling in skeletal muscle. Muscle-specific ablation of Baf155 increases oxidative metabolism by reducing HIF-1alpha 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-1alpha 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-1alpha, to activate HIF-1alpha signaling. Our findings reveal the crucial role of Baf155 in energy metabolism of skeletal muscle and the interaction between Baf155 and hypoxia signaling. |