Cell Reports
Volume 17, Issue 2, 4 October 2016, Pages 514-526
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Article
MyoD Regulates Skeletal Muscle Oxidative Metabolism Cooperatively with Alternative NF-κB

https://doi.org/10.1016/j.celrep.2016.09.010Get rights and content
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Highlights

  • MyoD regulates the oxidative metabolic capacity of adult skeletal muscle

  • ChIP-seq analysis identified MyoD binding on the PGC-1β, but not PGC-1α, gene locus

  • MyoD cooperates with alternative NF-κB to regulate PGC-1β transcription

  • MyoD and RelB co-occupy many other genes involved in aerobic respiration

Summary

MyoD is a key regulator of skeletal myogenesis that directs contractile protein synthesis, but whether this transcription factor also regulates skeletal muscle metabolism has not been explored. In a genome-wide ChIP-seq analysis of skeletal muscle cells, we unexpectedly observed that MyoD directly binds to numerous metabolic genes, including those associated with mitochondrial biogenesis, fatty acid oxidation, and the electron transport chain. Results in cultured cells and adult skeletal muscle confirmed that MyoD regulates oxidative metabolism through multiple transcriptional targets, including PGC-1β, a master regulator of mitochondrial biogenesis. We find that PGC-1β expression is cooperatively regulated by MyoD and the alternative NF-κB signaling pathway. Bioinformatics evidence suggests that this cooperativity between MyoD and NF-κB extends to other metabolic genes as well. Together, these data identify MyoD as a regulator of the metabolic capacity of mature skeletal muscle to ensure that sufficient energy is available to support muscle contraction.

Keywords

mitochondrial biogenesis
oxidative metabolism
skeletal muscle
MyoD
NF-kappaB
RelB
ppargc1b
PGC-1beta

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