Baf155 regulates skeletal muscle metabolism via HIF-1a signaling

Jong Seol Kang, Dongha Kim, Joonwoo Rhee, Ji Yun Seo, Inkuk Park, Ji Hoon Kim, Daewon Lee, Won Uk Lee, Ye Lynne Kim, Kyusang Yoo, Sunghwan Bae, Jongkyeong Chung, Rho Hyun Seong, Young Yun Kong

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Article numbere3002192
JournalPLoS Biology
Volume21
Issue number7 July
DOIs
StatePublished - Jul 2023

Bibliographical note

Publisher Copyright:
Copyright: © 2023 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Fingerprint

Dive into the research topics of 'Baf155 regulates skeletal muscle metabolism via HIF-1a signaling'. Together they form a unique fingerprint.

Cite this