Article ; Online: Baf155 regulates skeletal muscle metabolism via HIF-1a signaling.
2023 Volume 21, Issue 7, Page(s) 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, ...
| 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. |
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| MeSH term(s) | Animals ; Mice ; Gene Expression Regulation ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Muscle, Skeletal/metabolism ; Signal Transduction ; Transcription Factors/genetics ; Transcription Factors/metabolism |
| Chemical Substances | Hypoxia-Inducible Factor 1, alpha Subunit ; Transcription Factors ; Smarcc1 protein, mouse |
| Language | English |
| Publishing date | 2023-07-21 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2126776-5 |
| ISSN | 1545-7885 ; 1544-9173 |
| ISSN (online) | 1545-7885 |
| ISSN | 1544-9173 |
| DOI | 10.1371/journal.pbio.3002192 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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