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MyoD Regulates Skeletal Muscle Oxidative Metabolism Cooperatively with Alternative NF-κB
Journal article   Open access   Peer reviewed

MyoD Regulates Skeletal Muscle Oxidative Metabolism Cooperatively with Alternative NF-κB

Jonathan Shintaku, Jennifer M Peterson, Erin E Talbert, Jin-Mo Gu, Katherine J Ladner, Dustin R Williams, Kambiz Mousavi, Ruoning Wang, Vittorio Sartorelli and Denis C Guttridge
Cell reports (Cambridge), Vol.17(2), pp.514-526
10/04/2016
DOI: 10.1016/j.celrep.2016.09.010
PMCID: PMC5059110
PMID: 27705798
url
https://doi.org/10.1016/j.celrep.2016.09.010View
Published (Version of record) Open Access

Abstract

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. [Display omitted] •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 Shintaku et al. discovered that MyoD is a major regulator of skeletal muscle oxidative metabolism. MyoD and the alternative NF-κB transcription factor RelB cooperatively bind enhancers along the PGC-1β gene to regulate its transcription. In addition to PGC-1β, MyoD and RelB preferentially co-occupy numerous other oxidative metabolic genes.
 mitochondrial biogenesis MyoD NF-kappaB oxidative metabolism PGC-1beta ppargc1b RelB skeletal muscle

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